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Biomedical subjects

P Henriksson

Publications and source records attributed to P Henriksson.

At least 55 records · Page 3Linked to original sources
PubMed1991

Cost comparison of parenteral estrogen and conventional hormonal treatment in patients with prostatic cancer.

The present study compares the cost of antitumor therapy and adverse cardiovascular effects during the first year of treatment with oral estrogens, nonoral estrogens, or surgical castration in patients with prostatic cancer. We found a much higher cost for patients treated with orchidectomy and oral estrogens than for patients treated with nonoral estrogens. Twenty-five percent of the patients treated with oral estrogen suffered cardiovascular complications, compared to none of the patients treated by orchidectomy or nonoral estrogens. The initial cost of orchidectomy as compared to nonoral estrogen treatment was shown not be balanced within the expected survival time of patients with advanced prostatic cancer. Furthermore, surgical castration causes psychological trauma to the patient. We recommend parenteral estrogen therapy as a low-cost therapeutic regimen in patients with prostatic cancer.

Administration, Oral↗
PubMed1991

Prostacyclin production in myocardial infarction in the acute phase and during follow-up.

Twenty-five patients with myocardial infarction were monitored in the acute phase and during follow-up with regard to the in vivo production of prostacyclin (PGI2) and thromboxane (TxA2), by measurement of their major urinary metabolites, 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TxB2, respectively. In 22 of these patients PGI2 and TxA2 production were also assessed before, during and after an exercise test performed 6 weeks after discharge. In approximately 24% of patients the in vivo production of prostacyclin did not increase during the acute phase of the infarction process. This inability was usually associated with a decrease in the release of heart muscle enzymes, and was mostly frequently observed in women. During the exercise tolerance test, none of the patients showed any increase in prostacyclin production, in contrast to healthy volunteers, in whom a significant increase was seen. There were no differences between patients with and without an increase in prostacyclin production during the acute phase. At the follow-up 2 years after the myocardial infarction, eight cardiac events had occurred, all of which were noted among patients who exhibited an expected increase in prostacyclin production in association with the infarction. This would seem reasonable, since most of the patients in this group had larger primary infarctions.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Adenosine provokes myocardial ischaemia in patients with ischaemic heart disease without increasing cardiac work.

Intravenous infusion of adenosine in patients with ischaemic heart disease (IHD) has been shown to induce chest pain and ST-depression. The aim of this study was to determine whether such myocardial ischaemia could be due to an increase in myocardial work. Thus patients with stable angina pectoris (n = 8) were randomly allocated to exercise or adenosine infusion, with a 1-h rest period before the second test. The maximal tolerable work load was 120 +/- 13 W, where all patients but one experienced typical angina pectoris. ECG revealed ST-depressions in all patients. The maximal tolerable dose of adenosine was 108 +/- 6 micrograms kg-1 min-1. All patients experienced chest pain typical of habitual angina pectoris, and all but one developed ST-depressions. During exercise there was a gradual and marked increase in the rate pressure product (RPP), in parallel with the development of ST-depression. By contrast, during infusion of adenosine there was only a minor increase in RPP (P = 0.0001). In conclusion, infusion of adenosine provokes signs and symptoms of myocardial ischaemia in patients with IHD with only a minor increase in cardiac work compared to exercise. These results are consistent with the hypothesis of a myocardial steal.

Adenosine↗
PubMed1990

Thromboxane synthase inhibition: "endoperoxide shunt phenomenon" does not occur in healthy humans in vivo.

The effects of the thromboxane synthase inhibitor CGS13080 on the in vivo synthesis of thromboxane and prostacyclin were determined in six healthy volunteers. Two different doses (0.08 and 0.25 mg/kg x h) were infused for six hours under strictly controlled conditions and 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha were measured in urine using gaschromatography--mass spectrometry. The in vivo synthesis of thromboxane was inhibited by 80-75% while there was no effect on the in vivo prostacyclin synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Experimental atherosclerosis: effects of oestrogen and atherosclerosis on thromboxane and prostacyclin formation.

We evaluated the effect of oestrogen and experimental atherosclerosis on the in vivo formation of thromboxane and prostacyclin in rabbits. Twenty-four New Zealand White rabbits were divided into four groups. One group received control diet, one group received control diet and oestrogen, one group received control diet supplemented with 1% cholesterol and one group received cholesterol supplemented diet and oestrogen during 3 months. The in vivo formation of thromboxane and prostacyclin were measured as 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha in urine by gas chromatography/mass spectrometry. All rabbits on cholesterol diet became hypercholesterolaemic and developed atherosclerosis. As in previous experiments cholesterol and oestrogen-treated rabbits had only minor atherosclerosis compared to purely cholesterol-fed rabbits. The in vivo production of thromboxane in oestrogen-treated rabbits decreased from 1641 +/- 162 pg mg-1 creatinine pretreatment to 808 +/- 92 pg mg-1 creatine at 12 weeks (P = 0.0001). In contrast, the in vivo production of prostacyclin increased during oestrogen treatment (P = 0.0027). The in vivo production of prostacyclin decreased during pure cholesterol feeding without oestrogen 1384 +/- 219 pg mg-1 creatinine to 702 +/- 142 pg mg-1 creatinine (P = 0.0091). The ratio of in vivo prostacyclin to thromboxane formation increased 2-3-fold during oestrogen therapy (P = 0.0007).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of parenteral oestrogen on the coagulation system in patients with prostatic carcinoma.

Patients with prostatic carcinoma on oral oestrogen therapy have an altered coagulation system and suffer cardiovascular side effects. Oestrogens--especially oral oestrogens--are potent inducers of liver synthesised proteins, including coagulation factors. We have assessed the effect of non-oral oestrogen on the coagulation system in patients with prostatic carcinoma. Twelve patients were given monthly intramuscular injections of 320 mg polyoestradiol phosphate (PEP). No additional oestrogens were given. No change was found in any of the coagulation factors, including factor VII, with the exception of a significant decrease in antithrombin III. No patient, including 38 patients treated with PEP, had any cardiovascular complications after a mean follow-up period of 12.9 +/- 0.7 months; 76% of the patients responded to treatment. Parenteral administration of oestrogen caused a less marked change in the coagulation system than oral administration and should be the treatment of choice for prostatic carcinoma.

Antithrombin III↗
PubMed1990

Stanozolol and experimental atherosclerosis: atherosclerotic development and blood lipids during anabolic steroid therapy of New Zealand white rabbits.

Exogenous oestrogens have been shown to reduce low-density lipoprotein (LDL) cholesterol, increase high-density lipoprotein (HDL) cholesterol and reduce the severity of experimental atherosclerosis. In contrast, exogenous progestogens, testosterone and anabolic steroids have been shown to increase the level of LDL cholesterol and decrease the level of HDL cholesterol in man. We induced atheromatosis through cholesterol feeding of New Zealand White rabbits of 1% cholesterol (w/w) food supplementation for three months. Furthermore, control rabbits and cholesterol rabbits respectively, were given stanozolol 5 mg per day orally for the first 6 weeks and thereafter 10 mg per day. We found no significant influence of the anabolic steroid stanozolol either on the extent of atherosclerotic involvement or on HDL or LDL cholesterol. However, we could not exclude an influence of stanozolol on the development of atherosclerosis because of the finding that two out of 10 stanozolol-treated rabbits on normal diet developed macroscopic atherosclerosis compared to none out of 72 rabbits of the same age from previous studies given the same normal diet (p = 0.013).

Animals↗
PubMed1989

Hypocholesterolaemia and increased elimination of low-density lipoproteins in metastatic cancer of the prostate.

To study the influence of tumour mass on lipid metabolism, the lipoprotein pattern in untreated patients with newly diagnosed cancer of the prostate was examined. Total cholesterol levels were reduced in patients with evidence of metastasis (n = 30) compared with those without metastasis (n = 73). Since the major fraction of serum cholesterol is contained in low-density lipoproteins (LDL), turnover of LDL was studied in detail in 8 patients compared with 12 age-matched healthy men. LDL were cleared faster in the 3 patients with metastatic disease than in the patients without metastasis and in controls, indicating faster catabolism of LDL. Thus in prostatic cancer an increased tumour burden is associated with increased elimination of LDL, which contributes to reduced serum cholesterol levels.

Aged↗
PubMed1989

A comparison of androgen status in patients with prostatic cancer treated with oral and/or parenteral estrogens or by orchidectomy.

The effects of orchidectomy, combined oral/parenteral estrogen, and single-drug parenteral estrogen therapy on the serum levels of testosterone (T), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA) and its sulfate (DHAS), sex-hormone-binding globulin (SHBG), and albumin were studied in 48 patients with prostatic cancer. Both estrogen treatment regimens were as effective as orchidectomy in reducing circulating levels of T and A-4. Orchidectomy caused a slight decrease in DHAS levels. Oral estrogens profoundly decreased the serum levels of DHAS and, to a lesser extent, levels of DHA and of albumin, while parenteral estrogens had no effect in this respect. SHBG serum levels were highly increased by oral estrogens, slightly increased by parenteral estrogens, and unaffected by orchidectomy. The more pronounced effects of oral estrogens on circulating adrenal androgens may reflect an altered liver metabolism associated with this route of administration.

Administration, Oral↗
PubMed1989

Single-drug parenteral estrogen treatment in prostatic cancer: a study of two maintenance-dose regimens.

Treatment of 17 patients with prostatic cancer with 320 mg polyestradiol phosphate (PEP) as intramuscular injections every fourth week suppressed serum testosterone (T) values to orchidectomy levels within 1 month, and serum estradiol-17 beta (E2) rose to a mean level of 2,456 pmol/liter after 6 months. Following 6 months of treatment, the PEP dose was reduced to 80 mg/4 weeks in 9 and 160 mg/4 weeks in eight patients. Mean T levels, increased significantly after dose reduction in both groups and were above the upper orchidectomy limit at 1 month after dose reduction in the 80 mg group. Mean T levels, however, remained below this level at 5 months in the 160 mg group. Dose reduction caused a rise in gonadotropin levels in the 80 mg but not in the 160 mg group. While 320 mg/4 weeks may be a suitable initial dosage, doses less than or equal to 160 mg/4 weeks are insufficient as maintenance dosages if orchidectomy values of T are required.

Aged↗
PubMed1989

Estrogen therapy and liver function--metabolic effects of oral and parenteral administration.

Oral estrogen therapy for prostatic cancer is clinically effective but also accompanied by severe cardiovascular side effects. Hypertension, venous thromboembolism, and other cardiovascular disorders are associated with alterations in liver metabolism. The impact of exogenous estrogens on the liver is dependent on the route of administration and the type and dose of estrogen. Oral administration of synthetic estrogens has profound effects on liver-derived plasma proteins, coagulation factors, lipoproteins, and triglycerides, whereas parenteral administration of native estradiol has very little influence on these aspects of liver function.

Administration, Oral↗
PubMed1989

Effects of oestrogen therapy and orchidectomy on coagulation and prostanoid synthesis in patients with prostatic cancer.

Twenty patients with prostatic carcinoma were randomized to therapy with either oestrogens (n = 10) or orchidectomy (n = 10). Activators and inhibitors of coagulation were studied before treatment, 1.5 months and 6 months after the start of treatment. We found that the patients in the oestrogen group had already increased their factor VII level after 1.5 months (P less than 0.001) and this increased level persisted after 6 months. Factor X tended to increase after 1.5 months and this increase reached significance after 6 months (P less than 0.01). In the orchidectomy groups there was a significant increase in factor X at 6 months (P less than 0.01) and, in addition, antithrombin III (AT III) was increased at this time. Furthermore, there was a parallelism between the increase in factor VII and electrocardiographic evidence of increased coronary insufficiency (r = 0.60; P less than 0.025; n = 15). We found a significant increase of thromboxane as evidenced by the major urinary metabolite 2,3-dinorthromboxane B2 in the oestrogen group as compared to the orchidectomy group. In summary, patients with prostatic cancer during long-term oestrogen treatment were found to have increased levels of factor VII, factor VIII:C and fibrinogen. In addition these patients showed increased formation of thromboxane. The changes imply a hypercoaguable state and platelet activation. No such signs were found after orchidectomy. The findings in the oestrogen group might explain the continuously increased risk of cardiovascular complications during long-term oestrogen therapy.

Aged↗
PubMed1989

In vivo biosynthesis of thromboxane and prostacyclin during exposure to physiological levels of epinephrine.

The effects of 20-min epinephrine infusion (0.025 and 0.3 nmol/kg/min) on the in vivo synthesis of thromboxane A2 and prostacyclin were studied in ten healthy male volunteers. We assessed the in vivo biosynthesis of thromboxane A2 and prostacyclin by measurement of the urinary metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha, respectively. Epinephrine infusion did not cause any significant changes in the urinary excretion of the two metabolites. Thus, we conclude that physiological levels of epinephrine do not affect the in vivo biosynthesis of thromboxane A2 and prostacyclin.

Adult↗
PubMed1989

Oestrogen-induced changes in lipoprotein metabolism: role in prevention of atherosclerosis in the cholesterol-fed rabbit.

Administration of moderate pharmacological doses of oestrogen to cholesterol-fed rabbits for 12 weeks resulted in a dramatically retarded development of arterial lesions as compared to non-oestrogen-treated, cholesterol-fed rabbits (7% vs. 47% aortal involvement). Oestrogen treatment was associated with a retarded increase in plasma cholesterol, and five times higher high density lipoprotein (HDL) to very low density lipoprotein (VLDL) cholesterol ratio. Expression of hepatic lipoprotein receptor activity, as detected by heparin-releasable binding of 125I-hypercholesterolaemic VLDL, was heavily suppressed by cholesterol feeding. Administration of oestrogen modulated this response and resulted in higher receptor expression. In accordance, oestrogen treatment resulted in a less prominent reduction of 125I-hypercholesterolaemic VLDL clearance in the cholesterol-fed rabbits. VLDL from both groups of cholesterol-fed animals stimulated cholesteryl ester synthesis in cultured macrophages to the same extent. Thus, in rabbits under a dietary cholesterol load, oestrogen counteracted hepatic lipoprotein receptor suppression, reduced plasma VLDL- and increased plasma HDL-cholesterol levels, and to a large extent abolished the development of atherosclerosis.

Animals↗
PubMed1989

Patients at high risk of cardiovascular complications in oestrogen treatment of prostatic cancer.

The aim of this study was to predict cardiovascular complications in patients with prostatic cancer treated with oestrogen. A randomised prospective study of oestrogen therapy versus orchiectomy was performed. Patients with pre-existing cardiovascular morbidity were excluded (16%). Prior to the initiation of therapy, patients were subjected to exercise stress tests, physiological evaluation of peripheral circulation, blood volume estimation, chest X-ray, blood test, including hormones, lipoproteins, and antithrombin III, and a physical examination and history by a cardiologist. The oestrogen treatment and the orchiectomy group did not differ with regard to these pretreatment variables; 25% of the patients given oestrogen therapy had cardiovascular complications during the initial treatment year compared with none in the orchiectomy group. Three statistical discriminating techniques were employed and they allowed us to identify 2 strong discriminating variables for cardiovascular complications if oestrogen therapy is instituted in patients with prostatic cancer but without overt clinical cardiovascular disease. These 2 discriminators were luteinising hormone (LH) and ST-segment depression during exercise. This means that a patient with ST-segment depression during an exercise test and/or a high luteinising hormone concentration should not be treated with oestrogen.

Aged↗