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Biomedical subjects

A Himmelmann

Publications and source records attributed to A Himmelmann.

At least 55 records · Page 3Linked to original sources
PubMed1998

Isolated systolic hypertension: an important cardiovascular risk factor.

Hypertension is an established risk factor for cardiovascular disease morbidity and mortality. Randomized trials of antihypertensive therapy have demonstrated the benefits of treating diastolic blood pressure, and recently the value of treating isolated systolic blood pressure has also been established. There is an excess risk of cardiovascular disease in subjects with borderline isolated systolic hypertension. In fact, data from men screened for the Multiple Risk Factor Intervention Trial show that the great majority of excess deaths are in those with high-normal systolic blood pressure or with stage 1 hypertension, i.e., systolic blood pressure 130 to 159 mmHg. Similarly, data from the Framingham Heart Study and the Physicians' Health Study emphasize the importance of mild elevations of systolic blood pressure. As age increases the hemodynamic patterns of blood pressure change due to an increase in large artery stiffness, and borderline isolated systolic hypertension becomes the dominant form of hypertension. These facts make the prevention and control of borderline isolated systolic hypertension a key strategic challenge in the effort to prevent excess mortality attributable to blood pressure levels above normal.

Adult↗
PubMed1998

Carvedilol in the treatment of hypertension--a review of the clinical data base.

Carvedilol is a novel antihypertensive agent. It is a multiple-action neurohormonal antagonist with a beta-adrenoceptor blocking effect combined with a vasodilating action based on alpha1-adrenoceptor blockade. In addition, carvedilol exerts a number of well documented ancillary effects such as being a scavenger of free radicals. It also has an antiproliferative action on smooth muscle cells. This combination of effects opens up a number of interesting clinical perspectives. It is the purpose of this brief review to summarize some of the clinical studies that have been performed with carvedilol. Investigations in hypertensive patients will form the basis of this review, but special interest will also be devoted to other patient groups. In particular the therapeutic value of carvedilol will be discussed in patients with concomitant disorders such as atheromatosis, left ventricular hypertrophy, angina pectoris, myocardial infarction, congestive heart failure, arrhythmias, stroke, renal failure or diabetes. Finally, the usefulness of carvedilol in the treatment of elderly hypertensive patients will be reviewed. It is evident from the available scientific literature that carvedilol is an antihypertensive agent with a novel mode of action. It is effective in many of the subpopulations of patients alluded to above. It appears reasonable to assume that some of these therapeutic effects can be attributed to its ancillary properties.

Antihypertensive Agents↗
PubMed1998

Hypertension and long-term cancer incidence and mortality among Swedish men.

OBJECTIVE: To examine incidence of cancer and cancer mortality in relation to high blood pressure. DESIGN: A longitudinal study of middle-aged men from a random population sample. SETTING: Göteborg, Sweden. SUBJECTS: We studied 7396 men aged 47-55 years without diagnosed cancer at baseline (1970-1973). MAIN OUTCOME MEASURES: Incidence of cancer and mortality from cancer. RESULTS: By the end of December 1992, 1401 men had been diagnosed with cancer at any site and 651 had died from cancer. Of the men in the highest fifth of the systolic blood pressure distribution (above 166 mmHg) 126 per 10000 observation years were diagnosed with cancer at any site, compared with 91 per 10000 in the lowest fifth [below 130 mmHg; relative risk after adjustment for age, smoking, body mass index, treatment for hypertension and leisure time physical activity 1.41 (95% confidence interval 1.19-1.68); P for trend 0.0001]. Of men in the highest fifth, 55 per 10000 observation years died from cancer, compared with 42 in the lowest [adjusted relative risk 1.41 (1.09-1.82); P for trend 0.01]. Several types of tumour tended to be more common among men with hypertension, but only genito-urinary cancers [age-adjusted relative risk 1.39 (1.04-1.85)] and non-melanoma skin cancer [age-adjusted relative risk 1.98 (1.12-3.51)] were significantly so. Findings were similar for diastolic blood pressure and if data for the first 5 years of follow-up were excluded. There was an increase in risk of cancer also during the first 5 years [adjusted relative risk 1.80 (1.10-2.92) for systolic blood pressure and 1.77 (1.05-2.99) for diastolic blood pressure]. CONCLUSIONS: We found an excess risk of cancer and of death from cancer for men with high blood pressure. Although the increase in risk was comparatively modest, the findings are of public health importance, insofar as both hypertension and cancer are common conditions.

Aged↗
PubMed1998

Mitoxantrone in malignant pericardial effusion.

When occurring, malignant pericardial effusion (MPE) is usually a late phenomenon in most malignancies. Several treatment modalities, including chemotherapy, radiotherapy, pericardial window operation, pericardiotomy, catheter pericardiocentesis and local cytotoxic or sclerotherapy, have been employed. Mitoxantrone is reported as having potential in malignant pleural effusion. Between 1992-97, 5 patients (breast cancer-4 pts, ovarian cancer-1 pt) were admitted to the University Hospital of Tromsø due to a life-threatening MPE. They were all treated with ultrasound-guided pericardiocentesis followed by instillation of mitoxantrone (10 mg). Evaluation at a median follow-up of 59 days (range 28-294 days), 2 patients achieved CR, 1 PR and 2 patients have PD. Two patients are alive 213 and 294 days following therapy. Intrapericardial mitoxantrone instillation is a safe and simple way of handling MPE in malignancies sensitive to mitoxantrone.

Adult↗
PubMed1997

PU.1/Pip and basic helix loop helix zipper transcription factors interact with binding sites in the CD20 promoter to help confer lineage- and stage-specific expression of CD20 in B lymphocytes.

CD20 is a B-lineage-specific gene expressed at the pre-B-cell stage of B-cell development that disappears on differentiation to plasma cells. As such, it serves as an excellent paradigm for the study of lineage and developmental stage-specific gene expression. Using in vivo footprinting we identified two sites in the promoter at -45 and -160 that were occupied only in CD20+ B cells. The -45 site is an E box that binds basic helix-loop-helix-zipper proteins whereas the -160 site is a composite PU.1 and Pip binding site. Transfection studies with reporter constructs and various expression vectors verified the importance of these sites. The composite PU.1 and Pip site likely accounts for both lineage and stage-specific expression of CD20 whereas the CD20 E box binding proteins enhance overall promoter activity and may link the promoter to a distant enhancer.

Antigens, CD20↗
PubMed1997

Glucose and insulin levels in young subjects with different maternal histories of hypertension: the Hypertension in Pregnancy Offspring Study.

OBJECTIVE: To analyse whether hypertension during pregnancy is associated with early signs of impaired glucose metabolism in the offspring. DESIGN: Longitudinal study with a 5-year follow-up. SETTING: University Hospital, Göteborg, Sweden. MAIN OUTCOME MEASURES: Fasting levels of glucose, insulin and C-peptide. SUBJECTS: Thirty-six children were born to mothers with hypertension in pregnancy. The children were divided into two groups according to their mothers' blood pressure at follow-up 7-12 years after pregnancy. Nineteen children had hypertensive mothers (HT), while 17 children had normotensive mothers at follow-up (NT). A control group (C) comprised 16 children, who were born after normotensive pregnancies to mothers who remained normotensive. RESULTS: Fasting plasma glucose was significantly higher in HT than in NT (5.2 vs. 4.9 mmol L-1; P < 0.05). In C fasting glucose was 5.1 mmol L-1. The same trend was seen for fasting insulin in HT. NT and C, respectively (6.7 vs. 4.7 vs. 5.3 microU mL-1). The C-peptide level was 1.61, 155 and 1.64 ng mL-1, respectively. Calculated insulin resistance was 1.5 in HT. 1.0 in NT and 1.2 in C. CONCLUSIONS: It is suggested that hypertension during pregnancy may be associated with impaired glucose metabolism and elevated fasting glucose levels in the offspring during adolescence.

Blood Glucose↗
PubMed1996

Analysis of the Bruton's tyrosine kinase gene promoter reveals critical PU.1 and SP1 sites.

The gene defective in X-linked agammaglobulinemia (XLA) encodes a novel protein kinase termed Bruton's tyrosine kinase (Btk). Whereas the XLA phenotype is confined to abnormalities of B-cell development and function, Btk is expressed not only in B-lymphocyte lineage but also in myeloid lineage cells. The first 450 basepairs of the Btk promoter fused to a luciferase gene displayed a similar cell-type specificity. Critical binding sites for the transcription factors PU.1 and Sp1 were identified in the proximal portion of the Btk promoter upstream of a cluster of transcriptional start sites. Mutation of either the PU.1 or Sp1 site markedly reduced the activity of a Btk promoter-luciferase reporter construct in transfection experiments. In addition, PU.1 directly transactivated the Btk promoter, and deletion of the PU.1 binding site abolished this effect. This study implicates PU.1 and Sp1 as major regulators of Btk expression and provides a foundation for further study of the regulation of this gene in XLA patients that lack Btk mRNA.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1996

Haemodynamic effects and pharmacokinetics of oral d- and l-nebivolol in hypertensive patients.

OBJECTIVE: Nebivolol is a selective beta 1-adrenergic receptor blocker possessing an ancillary vasodilating effect. The objective of the present study was to study the haemodynamic and pharmacokinetic properties of nebivolol 5 mg once daily in a double-blind, placebo-controlled cross-over study. METHODS: Fifteen patients, 12 men and 3 women, with essential hypertension were investigated. Blood pressure and peripheral circulation were determined after acute oral nebivolol administration, 5 mg daily, and after 4 weeks treatment. RESULTS: The acute effect on blood pressure upon single-dosing was weak and non-significant. After 4 weeks both systolic blood pressure (152 vs 163 mmHg) and diastolic blood pressure (89 vs 97 mmHg) were significantly reduced after nebivolol treatment as compared to placebo. Following the first dose the venous volume was higher on placebo (5.88 ml.100 ml-1 tissue) as compared to active nebivolol treatment (5.17 ml.100 ml-1 tissue), while there were no statistically significant differences with regard to venous plethysmographic findings after 1 month on placebo (5.53 ml.100 ml-1 tissue) or on active treatment (5.97 ml.100 ml-1 tissue). Calculated peripheral resistance did not differ between active treatment (617 units) or placebo (548 units) after the first dose, whereas it was significantly lowered after 4 weeks of nebivolol treatment (483 units) as compared to placebo (593 units). CONCLUSIONS: Oral nebivolol 5 mg once daily lowered blood pressure and heart rate during steady state compared to placebo. Moreover, venous volume was reduced during acute but not steady-state dosing, while peripheral resistance was unaffected in the acute phase but reduced during steady state. Plasma concentrations of the separate enantiomers plus hydroxylated metabolites after the first and last dose in hypertensive patients were similar to those in healthy subjects.

Adrenergic beta-Antagonists↗
PubMed1996

Remikiren (Ro 42-5892)--an orally active renin inhibitor in essential hypertension. Effects on blood pressure and the renin-angiotensin-aldosterone system.

Remikiren (Ro 42-5892) is a new orally active renin inhibitor with high potency and specificity in vitro. In the present study, the drug was given in a short-term study in patients with essential hypertension, either as monotherapy or with added hydrochlorothiazide. Following a wash-out period of at least 3 weeks and then 8 days of single-blind placebo, 29 patients with essential hypertension were given remikiren 600 mg orally for 8 days. After 4 days of remikiren, hydrochlorothiazide 12.5 mg or 25 mg or placebo was added in double-blind fashion for the last 4 days. There were no significant changes in blood pressure in patients given remikiren alone. In patients given additional hydrochlorothiazide for 4 days, a marked reduction in blood pressure was observed. Remikiren effectively inhibited the plasma renin activity 24 h post-dose, whereas angiotensin II was reduced only during the first hours after drug administration. It is concluded that remikiren is orally effective. Its antihypertensive effect during short-term administration was not significant, but when given with a diuretic, a marked potentiation occurred. Further studies are needed to establish the long-term effects of remikiren alone and in combination therapy.

Antihypertensive Agents↗
PubMed1996

Long-term renal preservation in essential hypertension. Angiotensin converting enzyme inhibition is superior to beta-blockade.

Antihypertensive treatment is known to slow down the decline in glomerular filtration rate (GFR) with time. Angiotensin converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. In a recent prospective, randomized, double blind trial in 257 patients with essential hypertension, the loss of GFR, determined with 51Cr-EDTA clearance, was significantly less with an ACE inhibitor (cilazapril) than with a beta-adrenoceptor blocker (atenolol) during the first year of treatment. However, after 2 years, the two therapies were equally effective in this regard, thereby creating doubts about the long-term superiority of ACE inhibition in this regard. In order to elucidate whether the superior renal preservation with the ACE inhibitor was a transient effect, GFR was measured after 1 more year of treatment, i.e., after 36 months. At that time, the decline in GFR was significantly smaller in the ACE inhibitor group as compared to the beta-adrenoceptor blocker group (-3.0 [-5.5, -1.0; 95% CI] v -7.0 [-9.0, -4.5; 95% CI] mL/min x 1.73 m2; P = .026). This demonstrates that in the treatment of essential hypertension ACE inhibition preserves GFR significantly better than beta-adrenoceptor blockade during long-term therapy.

Adrenergic beta-Antagonists↗
PubMed1996

Hypertension in pregnancy and size at birth.

Low birth weight and high placental weight are associated with increased cardiovascular morbidity and mortality. Children born after hypertensive pregnancies have higher blood pressure than children born after normotensive pregnancies. Hypertension in pregnancy is considered a major risk factor for intrauterine growth retardation. The present study describes size at birth and perinatal characteristics in children born after hypertensive pregnancies. During five consecutive years 17,000 deliveries took place in the well defined geographic area of eastern Göteborg. Hypertension in pregnancy complicated 261 pregnancies. For comparison 260 normotensive pregnancies, matched for maternal age and time of delivery, were used. Standard deviation score for birth weight and length were calculated according to reference standards for birth weight (BWSDS) and length (BLSDS) based on all Swedish births 1977-1981 (n = 475,588). Children born after hypertensive pregnancies had lower birth weight, were shorter and had a shorter gestational period as compared with children born after normotensive pregnancies. Head circumference and placental weight did not differ and there were no significant differences in BWSDS. It is concluded that hypertensive pregnancies are characterized by lower birth weight and shorter gestational period. However, intrauterine growth retardation is not a general characteristic of hypertension in pregnancy.

Adolescent↗
PubMed1996

Long-term effects of losartan on blood pressure and left ventricular structure in essential hypertension.

In a 12-week, randomized, double-blind study, 24 patients with essential hypertension were given the angiotensin II antagonist losartan, or the beta-adrenoceptor blocker atenolol. Both drugs reduced blood pressure (BP) well, but losartan tended to reduce left ventricular mass (LVM) in contrast to atenolol. Following the double-blind phase 19 patients entered an open treatment period with losartan and additional treatment if BP was uncontrolled. LV structures were measured by echocardiography. The mean follow-up period was 29 +/- 2.6 (range 26-32) months. BP was reduced from 155.6 +/- 15.6/103.4 +/- 5.2 mm Hg to 131.3 +/- 10.5/82.7 +/- 3.3 mm Hg (P < 0.001). LV internal diameter was reduced (50.7 +/- 4.5 to 49.1 +/- 4.0 mm; P = 0.006), while there was an increase in interventricular septal thickness (10.2 +/- 1.1 to 11.2 +/- 1.3 mm; P = 0.001) and posterior wall thickness (10.0 +/- 0.9 to 10.6 +/- 1.1 mm; P = 0.023). Calculated LVM was not significantly altered during the follow-up period. In conclusion, losartan is effective in reducing BP during long-term treatment. No significant effect on LVM was observed, but there was an increase in LV wall thickness.

Adult↗
PubMed1995

ACE inhibition preserves renal function better than beta-blockade in the treatment of essential hypertension.

Antihypertensive treatment can slow down the decline in glomerular filtration rate (GFR) with time. In patients with diabetic nephropathy, angiotensin converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. Whether this applies to the much larger population of patients with essential hypertension is not yet known. In the present study, the effects of two different antihypertensive therapies on the loss of GFR with time, determined with Cr51-EDTA clearance after 6, 12 and 24 months of treatment, were assessed in a prospective, randomised, double-blind trial in 257 patients with essential hypertension. All had normal renal function and none had diabetes mellitus or glucosuria. Proteinuria (dipstick positive or trace) was detected in 7 patients initially. The two therapeutic modalities were the ACE inhibitor cilazapril and the beta-adrenoceptor blocking agent atenolol. Both therapies were equally effective in lowering systolic blood pressure (e.g. from 168 mmHg to 152 mmHg with cilazapril and from 170 mmHg to 155 mmHg with atenolol after 6 months, p < 0.001 for both). However, atenolol was slightly but significantly more effective in lowering the diastolic blood pressure at 6, 12 and 24 months. The decline in GFR with time was significantly smaller with cilazapril than with atenolol. After 6 months the reduction in GFR was 1.0 vs. 4.0 ml/min x 1.73 m2, p = 0.008 (cilazapril vs. atenolol) and after 12 months the corresponding changes were 2.0 vs. 4.5 ml/min x 1.73 m2, p = 0.04 and after 24 months 3.0 vs. 4.0 ml/min x 1.73 m2, respectively (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Efficacy and tolerability of tropisetron in comparison with a combination of tropisetron and dexamethasone in the control of nausea and vomiting induced by cisplatin-containing chemotherapy.

In a double-blind, randomised, multicentre study, the efficacy and tolerability of tropisetron and a combination of tropisetron and dexamethasone were compared for the control of nausea and vomiting induced by cisplatin in patients previously not entirely protected by tropisetron monotherapy. In all, 160 women with gynaecological cancers were studied during two consecutive courses of cisplatin-containing chemotherapy. During the first course (the screening course), all patients received tropisetron monotherapy [5 mg intravenous (i.v.) on day 1 and 5 mg orally on days 2-6] as antiemetic treatment. During the second course (the test course), tropisetron was compared with a combination of tropisetron and dexamethasone (20 mg i.v. on day 1 and 4.5 mg twice daily on days 2-6). This part of the study was double-blind, randomised and placebo-controlled. Candidates for randomisation were patients with partial control of nausea (< 12 h of nausea) or partial control of vomiting (1-4 episodes of vomiting) during the screening course. Patients with complete control of nausea and vomiting in the screening course continued with tropisetron monotherapy; patients with treatment failure received open rescue treatment in course 2. Total control of acute nausea was achieved in 37% of the tropisetron + placebo group and in 75% of the tropisetron + dexamethasone group (P = 0.001). Significantly more patients on tropisetron-dexamethasone than on tropisetron-placebo were also free of delayed nausea. Acute vomiting was prevented in 40% of the patients in the placebo group and in 75% in the dexamethasone group (P = 0.001). Delayed vomiting was also significantly less frequent in dexamethasone-treated patients than in placebo-treated patients. Tropisetron was well tolerated both as monotherapy and in combination with dexamethasone. The most frequent adverse events were headache (34%), constipation (12.5%) and fatigue (12.5%). Adding high doses of a corticosteroid did not induce further adverse events or disregulate concurrent diseases.

Adult↗