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Biomedical subjects

P Henriksson

Publications and source records attributed to P Henriksson.

At least 19 recordsLinked to original sources
PubMed2000

Parenteral estrogen versus total androgen ablation in the treatment of advanced prostate carcinoma: effects on overall survival and cardiovascular mortality. The Scandinavian Prostatic Cancer Group (SPCG)-5 Trial Study.

OBJECTIVES: To compare the effect on overall survival of total androgen ablation (TAA) with that of parenteral estrogen and to pay special attention to cardiovascular mortality. TAA (orchiectomy or a luteinizing hormone-releasing hormone analogue combined with an antiandrogen) has been proposed as superior to other endocrine treatments for patients with prostate carcinoma. Recently, the use of parenteral estrogen has been suggested to reduce or even negate the well-known cardiovascular side effects of oral estrogens. METHODS: Nine hundred fifteen patients were randomized to intramuscular injections of 240 mg polyestradiol phosphate (PEP) every second week for the first 8 weeks (5 doses) followed by a maintenance dose of 240 mg every month (n = 458) or to bilateral orchiectomy or triptorelin 3.75 mg every month combined with the antiandrogen flutamide 250 mg three times daily. The choice between orchiectomy and triptorelin was at the discretion of the clinician and patient. Patients were stratified according to performance status, presence of cardiovascular disease, and alkaline phosphatase level. An observer totally unaware of the treatment given classified all deceased patients. RESULTS: At a median follow-up of 18.5 months, no signs of a difference in overall survival were found between TAA and PEP (P <0.001). Of 458 patients, 266 (58.1%) had died in the PEP group compared with 269 (58.9%) of 457 patients in the TAA group. Within the TAA group, no difference in overall survival existed between patients who had undergone orchiectomy or who were given triptorelin. Furthermore, no differences in cardiovascular mortality were found (3.5% in the PEP group and 3.1% in the TAA group). CONCLUSIONS: The current parenteral estrogen regimen seems to be of comparable efficacy and cardiovascular safety as TAA in terms of overall survival. PEP has by far the lowest drug cost and also the lowest cumulative direct costs and thus has the highest cost-effectiveness. We suggest that parenteral estrogen be included as a therapeutic option in the endocrine management of prostate carcinoma.

Aged↗
PubMed1999

Time for revival of estrogens in the treatment of advanced prostatic carcinoma? Pharmacokinetics, and endocrine and clinical effects, of a parenteral estrogen regimen.

BACKGROUND: The present pilot study tested the clinical performance of a new pharmacokinetically guided dosing regimen of parenteral estrogen in patients with advanced prostatic carcinoma. The aim was to accelerate endocrine effects and to avoid cardiovascular side effects. METHODS: Seventeen patients were randomized to intramuscular injections of 240 mg polyestradiol phosphate (PEP) every second week for the first 8 weeks (five doses), followed by a maintenance dose of 240 mg every month; and 16 patients were randomized to bilateral orchidectomy. The estrogen dosing was calculated by pharmacokinetic modelling to achieve a rapid increase in serum estradiol and thereby a fast decrease in testosterone. RESULTS: The predicted increment in serum estrogen was achieved, together with a subsequent decrease in testosterone in the PEP group. In addition, there were no signs of an increased cardiovascular morbidity. This was probably due to a minimal estrogenic influence on the liver and was reflected by unchanged levels of coagulation factor VII. Clinical effects, during the first 2 years of treatment, were similar in the two treatment arms, with 12 patients in the orchidectomy group and 14 patients in the PEP group responding to treatment. CONCLUSIONS: The present parenteral regimen is an efficient and time-saving estrogen regimen with a favorable side-effect profile. PEP seems to offer a potential for revival of the most cost-effective endocrine treatment of cancer of the prostate, i.e., estrogen.

Aged↗
PubMed1999

A single high dose of vitamin C counteracts the acute negative effect on microcirculation induced by smoking a cigarette.

Cigarette smoking is associated with marked acute changes in microcirculation including reduced blood flow. We tested the hypothesis that the reduced blood flow velocity is due to the imbalance between prooxidants and antioxidants that occurs as a consequence of smoking and that it can be reduced by an antioxidant. The effect of smoking a single cigarette on nail-fold microcirculation was analyzed in 24 healthy subjects with varying smoking habits. Vital capillary microscopy was used and the blood cell flow velocity in the capillaries was evaluated before and 1-30 min after smoking. Smoking induced a marked decrease in microcirculatory blood flow in 23 of the 24 subjects (40-50% decrease 1-5 min after smoking). This change was reduced by more than 50% in the same subjects after intake of 2 g of vitamin C 2 h before smoking (P < 0.0001 by ANOVA test) with smokers responding similarly to nonsmokers in these experiments. Intake of 1 g of vitamin C had no significant effect on the smoking-induced changes in most of the subjects tested (n = 11). Pretreatment with aspirin had little or no effect on the response to smoking (n = 9). Our results show that treatment with a single high dose of vitamin C can reduce and in some individuals even completely abolish the negative acute effect on microcirculation induced by smoking a single cigarette. This effect of vitamin C is not likely to be mediated by the cyclooxygenase system.

Adult↗
PubMed1999

Costs of coronary heart disease and stroke: the case of Sweden.

OBJECTIVES: To estimate the annual costs in Sweden of coronary heart disease (CHD) and stroke, and the potential cost savings if these clinical 'events' are avoided. The analysis is undertaken from a societal perspective, including both direct and indirect costs. Costs are calculated for five clinical conditions: (i) acute myocardial infarction (AMI), (ii) angina pectoris (AP), (iii) unstable angina (UA), (iv) congestive heart failure (CHF), and (v) stroke. DESIGN: A retrospective study including patients admitted to the Department of Medicine at Södertälje Hospital during the period January 1993 to March 1995 with CHD or a stroke. Each patient was followed for 1 year after admission to the hospital. To estimate potential cost savings, the patient was used as his or her own control. The potential savings in direct costs if CHD or a stroke is avoided were estimated as the difference between costs for 1 year after and 1 year before the event. The indirect costs were calculated as the difference between the values of market production of goods and services the year before the event and the year after. SETTING: The Department of Medicine at Södertälje Hospital, Södertälje, Sweden. SUBJECTS: The patients included in the study were patients at the Department of Medicine at Södertälje Hospital in Sweden. The inclusion criterion was that the patients should have been admitted for the first time for CHD or stroke during the year 1994. To obtain 25 patients for each clinical category we first had to expand the inclusion period to cover January 1993 to March 1995. Secondly, we also had to include 36 patients with an earlier established uncomplicated CHD or stroke. Despite this, no more than 22 patients with UA were found. INTERVENTIONS: Patients were followed in medical practice. MAIN OUTCOME MEASURES: Costs, direct and indirect costs, and potential savings. RESULTS: The mean direct costs during the year after a clinical event range between Swedish kronor (SEK) 41 000 for CHF and SEK 96 000 for stroke, whereas the mean potential savings in direct costs range from SEK 36 000 for CHF to SEK 91 000 for UA. The potential mean savings in indirect costs range between SEK 24 000 for CHF and SEK 102 000 for AMI. The direct costs for first-time patients are lower than those for patients with an earlier established CHD or stroke. No systematic differences have been found in potential direct cost savings and indirect costs between the two patient groups. CONCLUSIONS: CHD and stroke are associated with high costs during the year after admission to the Department of Medicine. There are also large potential cost savings from the prevention of CHD and stroke. However, further studies, including more patients and costs arising in the municipality, are needed to establish more precise and complete estimates of the costs related to CHD and stroke.

Aged↗
PubMed1999

Incorporation of wild-type and C-terminally truncated human epidermal growth factor receptor into human immunodeficiency virus-like particles: insight into the processes governing glycoprotein incorporation into retroviral particles.

Previous results have indicated that incorporation of surface glycoprotein into retroviral particles is not a specific process and that many heterologous viral and cellular glycoproteins can be incorporated as long as they do not have long cytoplasmic C-terminal regions which were presumed to be sterically inhibitory. In this study, this concept has been directly examined by analyzing the incorporation of the wild-type human epidermal growth factor receptor (Wt-EGFR) and of a C-terminally truncated mutant of Wt-EGFR (Tr-EGFR) into human immunodeficiency virus (HIV)-like particles. Incorporation was directly analyzed at the protein level and by immunogold labelling of enriched HIV-like particles. In agreement with the above concept, Tr-EGFR, with only 7 C-terminal amino acids (aa), was efficiently incorporated into HIV-like particles. Incorporation of the Wt-EGFR species, with 542 C-terminal cytoplasmic aa, was reduced by a factor of about 5 in comparison to that of the Tr-EGFR species. However, the Wt-EGFR species was still very significantly present in the HIV-like particles. A series of control experiments verified that this represents genuine incorporation of Wt-EGFR into the membrane of HIV-like particles. These observations allow further speculation as to the processes governing glycoprotein incorporation into retroviral particles and indicate that the internal virus structure of HIV (in particular the matrix layer [MA]) can accommodate much larger heterologous cytoplasmic domains in incorporated glycoproteins than previously assumed.

Cell Line↗
PubMed1998

Inhibition of cellular glycoprotein incorporation into human immunodeficiency virus-like particles by coexpression of additional cellular interaction partner.

We examined the concepts of whether cellular surface glycoprotein overexpressed in heterologous cells can be efficiently incorporated into lentiviral particles and whether incorporation is blocked when a natural interaction partner is coexpressed. Human CD4 and a truncated version lacking the cytoplasmic C terminus, expressed in 293T cells, were efficiently incorporated into Env-defective human immunodeficiency virus type 1 virus-like particles. However, on coexpression of p56(lck), the natural binding partner of the CD4 C-terminal domain in T lymphocytes, incorporation of the wild-type CD4 was completely abolished, whereas incorporation of the C-terminally truncated mutant remained unaffected. Confocal microscopy and detergent solubility assays did not reveal any significant difference in the distribution of wild-type CD4 at the plasma membrane in the presence or absence of p56(lck). These results give some insight into the processes governing protein incorporation into the lipid bilayer of lentiviruses.

Alkaline Phosphatase↗
PubMed1998

[Homozygous protein C deficiency can be detected by prenatal diagnosis].

Homozygous protein C deficiency (HPCD) with purpura fulminans is a rare condition with an estimated incidence of 1-2 per 400,000 births. About 20 case reports have appeared since the first one was published in 1983. HPCD provides an excellent illustration of the fundamental importance of the protein C anticoagulant pathway. This severe coagulopathy results in serious organ damage, often already in utero, and without treatment it is incompatible with life. The treatment options include fresh frozen plasma and protein C concentrate in the acute phase, followed by oral anticoagulant therapy. Over 160 different point mutations in the protein C gene have been identified in recent years, offering new possibilities for prenatal diagnosis. The article describes the case of a family who lost two children with congenital HPCD. But where the specific point mutation was identified thus enabling prenatal diagnosis to be performed in a subsequent pregnancy.

Adult↗
PubMed1998

Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double-blind placebo-controlled study.

OBJECTIVE: To study whether intravenous nitroglycerin (NTG) reduces the incidence of ischaemic events and leucocyte activation, as well as inhibiting platelet aggregation in patients with unstable angina pectoris. DESIGN: Randomized double-blind placebo-controlled study. SUBJECTS: One hundred and sixty-two patients with a history and electrocardiographic changes suggesting unstable angina pectoris. INTERVENTIONS: A 48-hour titrated intravenous infusion of NTG or placebo. RESULTS: Of the 162 randomized patients, 19 were excluded because of an acute myocardial infarction on randomization (11 patients) or proven presence of a non-ischaemic cause of the pain (6 patients). Other causes (2 patients). No differences in the clinical findings were detected between the groups on randomization. In the comparison of NTG and placebo, fewer patients in the former group had more than two new attacks of chest pain lasting for < 20 min or one new attack of chest pain lasting > 20 min, despite sublingual NTG (13/25, P < 0.03). In addition, the attacks of pain lasting > 20 min in the NTG group were delayed compared to those in the placebo group (P < 0.05), suggesting a beneficial effect on these more severe episodes. Fewer patients in the NTG group required more than two sublingual NTG tablets (P < 0.005). NTG also reduced the rate-pressure product (P < 0.05), compared to placebo after 2 h but not after 24 h. Compared to baseline, platelet aggregation was inhibited in the patients who had received an NTG infusion for 2 h (P < 0.05). In both groups, leucocytes were activated at baseline, but remained unchanged thereafter. CONCLUSIONS: Intravenous NTG seems to reduce myocardial ischaemia in patients with unstable angina pectoris more than the placebo.

Adult↗
PubMed1997

Possible bone-preserving capacity of high-dose intramuscular depot estrogen as compared to orchidectomy in the treatment of patients with prostatic carcinoma.

BACKGROUND: Treatment of prostatic disease with GnRH agonists or by orchidectomy affects bone mass negatively. Estrogen treatment has beneficial effects on bone mass in women and might hypothetically have a bone preserving capacity also in patients with prostatic cancer. METHODS: We followed serum markers for bone and collagen metabolism and sex steroids for 18 months in patients with prostatic cancer treated by orchidectomy (N = 13) or by single-drug parenteral polyestradiol phosphate (240 mg intramuscularly every second week for the first two months, and then every fourth week; N = 17). RESULTS: Total and free testosterone reached castration levels within 1.5 months of estrogen treatment. Four patients developing progressive disease and/or signs of metastasis were excluded from the analysis. In the remaining patients, serum osteocalcin, procollagen IIIP (PIIINP), procollagen (PICP), and the crosslinked carboxyterminal telopeptide of type I collagen (ICTP) increased significantly over time following orchidectomy (N = 11). Serum osteocalcin and PICP decreased significantly over time during estrogen treatment (N = 15). Treatment values of all four markers were significantly lower in estrogen-treated than in orchidectomized patients. CONCLUSIONS: The changes in serum bone and collagen markers indicate an increased bone turnover in orchidectomized subjects. The opposite pattern was found in the estrogen-treated patients, indicating a reduced turnover. Estrogens may also have a bone mass-preserving capacity in elderly males with prostatic cancer.

Aged↗
PubMed1997

Use of a hormone-sensitive (LNCaP) and a hormone-resistant (LNCaP-r) cell line in prostate cancer research.

BACKGROUND: In order to develop a hormone-resistant analog to the hormone sensitive cell-line LNCaP, different methods were tried. METHODS: After almost one year of continuous culture in RPMI-1640, containing a low concentration of androgens, the hormone sensitive cell-line LNCaP became hormone resistant and was named LNCaP-r. RESULTS: We used the LNCaP/LNCaP-r model system in order to study methods for the parenteral treatment of prostate carcinoma with estrogens, to study the mechanism of action of estramustine, and to identify markers useful as predictive tests for prostate carcinoma. CONCLUSIONS: A model system made up of the hormone sensitive prostate LNCaP cell-line and the hormone resistant LNCaP-r subline was developed and characterized. This system is, despite a number of limitations, easy to use as a first step to test different hypotheses that can be studied further in later clinical trials.

Androgens↗
PubMed1997

The impact of hormone replacement therapy on quality of life and willingness to pay.

OBJECTIVE: To measure the gain in quality of life due to hormone replacement therapy for women with mild and severe menopausal symptoms. DESIGN: Prospective study where data on quality of life and willingness to pay were collected by interview. SETTING: Department of Gynaecology at Södertälje Hospital near Stockholm. PARTICIPANTS: One hundred and four women aged 45 to 65 years treated for menopausal symptoms for at least one month. METHODS: Quality of life was measured by the time tradeoff and rating scale methods. The willingness to pay for hormone replacement therapy was investigated using the contingent valuation method. MAIN OUTCOME MEASURES: The quality adjusted life year weight measured with the rating scale and time tradeoff methods, and willingness to pay. RESULTS: The increase in the quality adjusted life year weight due to hormone replacement therapy for women with mild symptoms was 0.26 according to the rating scale method and 0.18 according to the time tradeoff method. For women with severe symptoms the quality adjusted life year weight increased by 0.50 according to the rating scale method and by 0.42 according to the time tradeoff method. The mean willingness to pay for hormone replacement therapy per month was 2300 Swedish krone for women with mild symptoms and 4800 Swedish krone for women with severe symptoms (Pounds 1 = 10.3 Swedish krone). CONCLUSIONS: Hormone replacement therapy leads to a major improvement in quality of life for women with menopausal symptoms. Both for women with mild and severe menopausal symptoms the willingness to pay for the treatment also greatly exceeds the costs, indicating that hormone replacement therapy is economically beneficial for women with menopausal symptoms.

Aged↗
PubMed1997

Vitamin C reduces cholesterol-induced microcirculatory changes in rabbits.

The microcirculation was studied for 10 weeks in untreated rabbits (n = 12) and in rabbits treated with vitamin C in their drinking water (0.5 g/d; n = 6), a 1% cholesterol diet (n = 12), or a combination of the two treatments (n = 11). The studies were performed by direct intravital microscopic imaging of the conjunctiva of both eyes to evaluate blood flow velocity, microvessel diameter, and microhemorheologic conditions. As we reported previously, changes occurred in all of the aforementioned variables as a consequence of cholesterol feeding. After 3 and 6 weeks of feeding, there was a marked and significant (P < .0001) decrease in blood flow velocity in third-order arterioles, which was accompanied by stasis and erythrocyte aggregation in the smaller conjunctival vessels. When cholesterol treatment was combined with vitamin C, blood flow was almost identical to that of controls and significantly (P < .0001) higher than that of rabbits treated with cholesterol alone. All other changes were also significantly reduced by the addition of vitamin C treatment to the cholesterol diet. Cholesterol-treated rabbits developed macroscopic arterial lesions that were not significantly reduced by vitamin C treatment. Neither circulating oxysterol levels nor atheromas were reduced by vitamin C treatment, which also had no significant effect on lipid or circulating vitamin E levels. We have previously shown that the lipid-soluble antioxidant BHT is able to prevent both cholesterol-induced microcirculatory changes and the development of arterial lesions in rabbits. This phenomenon is compatible with a critical oxidation step occurring in the lipid phase that is common to both processes. The finding that microcirculatory changes can be prevented by a water-soluble antioxidant is compatible with a role for water-soluble oxidants in this context. The possibility is discussed that vitamin C might also be important for the microcirculation in humans.

Animals↗
PubMed1997

Focused quality improvement in health care: the quality, satisfaction, performance technique applied in internal medicine.

Service quality assessments are dominated by simple analysis of questionnaire data. Such methods generally lack validity and reliability. Moreover, they do not have a target side defining what actions patient satisfaction should lead to from a management point of view. The quality, satisfaction, performance method, a technique with high validity, was applied in an internal medicine setting. The method appears to offer a unique way to relate desired results of care to different processes and structures in the clinic as well as incentives to intervene to improve the quality of care.

Chest Pain↗
PubMed1996

Dietary cholesterol induces transient changes in plasma nitrate levels in rabbits that are correlated to microcirculatory changes.

Dietary treatment of rabbits with 1% cholesterol resulted in a transient rise in their plasma nitrate levels. After 3 weeks of treatment the nitrate levels were about 50% higher than those of the controls (p<0.005). After 10 weeks of treatment the nitrate levels were similar to those at the start of the study. In accordance with previous work (Xiu et al., J. Clin. Invest., 1994, 93, 2732-2737), the cholesterol treatment let to a decreased blood flow velocity in arterioli of the third order in the conjunctiva, and a decreased diameter of these arterioli. There was a significant correlation between plasma nitrate levels and the two microcirculatory variables (p<0.0001). Nitrate is the major metabolic end product of nitric oxide (NO), and plasma nitrate levels may be used as an index of the endogenous formation of NO. The present results suggest that dietary cholesterol induces a transient increase in the synthesis of NO. Such an increased synthesis may compensate for part of a cholesterol-induced degradation of NO.

Animals↗
PubMed1996

Profound decrease of in vivo formation of thromboxane during oestrogen therapy.

Oestrogen has been proposed to influence platelet activity and formation of the vasoactive eicosanoids thromboxane and prostacyclin. Previous studies have been based on ex vivo techniques with well-known artifacts during blood sampling and ex vivo conditions. The present study is the first to assess in vivo formation through gas chromatographic/mass spectrometric analysis of the major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-PGF1 alpha. Ten consecutive male patients with prostatic carcinoma participating in a randomized study comparing the effects of parenteral oestrogen therapy (n = 5) with orchidectomy (n = 5) were included. Oestrogen was given as polyestradiol phosphate 240 mg i.m. every month, 2,3-dinor thromboxane B2 and 2,3-dinor-6-keto-PGF1 alpha were analysed with the help of tetradeuterated internal carriers/standards. We found a consistent decrease of in vivo formation of thromboxane by approximately 40% during parenteral oestrogen therapy (P = 0.008) and a doubling after surgical castration. The ratio of prostacyclin to thromboxane increased by approximately 50% (P = 0.023) during oestrogen therapy. In conclusion, oestrogen induced a marked decrease of in vivo formation of thromboxane and a marked increase in the ratio of prostacyclin to thromboxane formation in all patients. According to current knowledge this should be beneficial for the cardiovascular system. Furthermore, thromboxane formation increased after surgical castration. The latter fact should direct attention to the influence of androgens on thromboxane synthesis. Our findings discloses a marked sex-hormone sensitivity of the thromboxane-forming system.

Aged↗
PubMed1996

Hormonal regulation of serum lipoprotein (a) levels: effects of parenteral administration of estrogen or testosterone in males.

When given orally, estrogens, as well as androgens, lower serum lipoprotein (a)[Lp(a)]levels. To determine whether these effects occur also after parenteral administration of steroids, Lp(a) levels were determined in two groups of elderly males suffering from prostatic carcinoma, who were randomized to treatment with parenteral estrogen (n = 8) or orchidectomy (n = 6). One group of healthy male volunteers (n = 9) was studied after parenteral administration of testosterone. Estrogen was given as im polyestradiol phosphate, 240 mg twice monthly, and testosterone was given as im injections, 250 mg/week. In the orchidectomized subjects, Lp(a) levels increased by 20% by month 3 after treatment (P < 0.05). In spite of drastic changes in serum hormone levels, no change in Lp(a) levels was observed in the estrogen-treated subjects. Concomitantly, low-density lipoprotein cholesterol levels were lowered by 15% and high-density lipoprotein cholesterol levels increased by 20%. Testosterone administration lowered Lp(a) levels by 20% (P < 0.05). No significant changes in serum lipid levels were observed in the testosterone-treated subjects or in the orchidectomy group. Thus, during parenteral administration of estrogens or androgens, diverging effects on Lp(a) and serum lipoproteins were observed. In particular, the mode of administration of estrogen influenced the response in Lp(a) levels. This suggests that the regulatory role of sex hormones on serum Lp(a) levels may depend on their capability to influence hepatic metabolic pathways of Lp(a).

Adult↗