PubMed Health⌕ Search

Biomedical subjects

Thomas Hedner

Publications and source records attributed to Thomas Hedner.

At least 19 recordsLinked to original sources
PubMed2005

Pentane-1,5-diol as a percutaneous absorption enhancer.

Propylene glycol (propane-1,2-diol) is the only diol widely used in dermatology. Pentane-1,5-diol is mainly used as a plasticizer in cellulose products and adhesives, in dental composites and in brake fluid compositions and as a preservative for grain. However, pentane-1,5-diol is also an effective solvent, water-binding substance, antimicrobial agent and preservative and may therefore replace several ingredients in a skin composition. The release of tri-iodothyroacetic acid (TRIAC) and percutaneous absorption of hydrocortisone and mometasone furoate with either pentane-1,5-diol or propane-1,2-diol and 2-methyl-pentane-2,4-diol (hexylene glycol), respectively, as enhancers was compared. The release of TRIAC was 21% higher when pentane-1,5-diol was used as an enhancer instead of propane-1,2-diol. The percutaneous absorption of hydrocortisone through the skin was increased 12 times with propane-1,2-diol compared to 4.4 times with pentane-1,5-diol. However, the percutaneous absorption of hydrocortisone into the skin was 50% higher with pentane-1,5-diol compared to propane-1,2-diol. There was no significant difference, between the original mometasone furoate cream, with 2-methyl-pentane-2,4-diol, and the new cream with pentane-1,5-diol in the amount of mometasone furoate that was absorbed into the skin and through the skin. However, the cosmetic properties of the new mometasone furoate cream was superior to the original mometasone furoate cream, for examples, no bad odour, more even texture, goes better into the skin and has less greasiness. Pentane-1,5-diol can be used as a technology platform, which adds a series of desirable properties to dermatological preparations and enhances product usability. This will result in improved formulations for a series of major and commonly used dermatological drugs. When used in pharmaceutical topical preparations, pentane-1,5-diol will increase the percutaneous absorption of the active substance and it is an efficient antimicrobial agent that will act as an effective preservative in topical formulations. Pentane-1,5-diol is cosmetically attractive, has low risk for skin and eye irritation compared to other diols, low toxicity risk and no bad odour.

Administration, Cutaneous↗
PubMed2005

The in vitro activity of pentane-1,5-diol against aerobic bacteria. A new antimicrobial agent for topical usage?

Multi-resistance to antibiotic therapy and to biocides is becoming increasingly common, which has led to mounting concern worldwide regarding the future use of traditional antimicrobials. Diols or glycols also have antimicrobial effects. Pentane-1,5-diol has low oral toxicity, is essentially non-irritating to the skin and has high antimicrobial activities against bacteria, fungi and viruses. The effect of pentane-1,5-diol against both sensitive and multi-resistant Gram-positive and Gram-negative bacteria was tested in vitro against 85 bacterial strains showing minimal inhibitory concentrations in the range of 2.5 to 15.0% (vol/vol) against both antibiotic-susceptible and multi-resistant aerobic bacteria. The exact mechanism of action is unknown but probably pentane-1,5-diol sucks water out of the bacterial cells which then collapse, a mechanism to which it is probably very difficult to develop resistance. The high activity against multi-resistant bacteria makes pentane-1,5-diol an interesting new compound for topical antimicrobial therapy in humans.

Administration, Cutaneous↗
PubMed2005

Cost analysis of different pharmacological treatment strategies in elderly hypertensives.

OBJECTIVE: To compare costs for management of hypertension in elderly hypertensives randomized to starting treatment with conventional (beta-blockers/diuretics) therapy or a therapy initiated with a calcium antagonist or an angiotensin-converting enzyme (ACE) inhibitor. DESIGN: Health economic substudy in the Swedish Trial in Old Patients with Hypertension-2 (STOP Hypertension-2). SETTING: Outpatient clinics in Sweden. In this health economics substudy, 16/312 participating STOP-2 trial centers were selected. SUBJECTS: Elderly (70--84 years) patients (n=303) with a systolic and/or diastolic hypertension (or=180 and/or 105 mmHg). METHODS: Costs for patient management were analyzed and categorized in costs for routine care (protocol-driven costs, PDC), costs for extra visits or care (non-protocol-driven costs, NPDC), and direct drug costs (drug treatment costs, DTC). All calculations are related to costs during the first year of treatment after inclusion in STOP Hypertension-2. RESULTS: Out of the scheduled visits, a total of 99% were actually performed by the patients. There were no differences in the number of visits between the three treatment groups (diuretics/beta-blockers, calcium antagonists or ACE inhibitors). PDC did thus not differ between the three treatment groups. NPDC were similar in the conventional and calcium antagonist groups and lower than for the ACE inhibitor group. DTC were lower in the conventional treatment group compared with the other two groups. CONCLUSION. In elderly hypertensives in STOP Hypertension-2, total costs for management of hypertension were lower in patients assigned to diuretics, beta-blockers or calcium antagonists compared with ACE inhibitors during the first year of treatment. These results may be relevant to management of elderly hypertensive patients, especially in those patients without compelling indications or contraindications to starting treatment with either of these three main drug alternatives. Notably, with a specific drug regimen there are sizable NPDC such as extra visits and controls associated with symptoms or side-effects of a specific therapy, which significantly add to the total costs of treatment. Such costs, beyond the actual costs for the drugs, are important to realize and evaluate in order to provide the true costs for treatment of hypertensive patients.

Aged↗
PubMed2004

Association between the low activity genotype of catechol-O-methyltransferase and myocardial infarction in a hypertensive population.

AIM: Estrogens regulate several biological processes involved in the pathogenesis of myocardial infarction. Catechol-O-methyltransferase (COMT) is a key enzyme in the degradation of estrogens. There is a functional polymorphism in the COMT gene (Val158Met), affecting the activity of the enzyme. We investigated if the low activity genotype of COMT is associated with an altered risk of myocardial infarction. METHODS AND RESULTS: In a prospectively followed hypertensive cohort we identified 174 patients who suffered a myocardial infarction during the study and compared them to 348 controls from the same cohort. The COMT polymorphism and serum levels of sex hormones were analysed. Patients homozygous for the low activity COMT genotype had a decreased risk of myocardial infarction compared to those with the high activity genotype, odds ratio 0.65 (95% CI 0.44-0.97, p=0.033 ). The protective effect of the low activity genotype was most evident among older patients (> 58 years of age), odds ratio 0.43 (95% CI 0.23-0.79, p=0.006 ). Serum levels of estradiol were increased ( p=0.006 ) in males with the low activity genotype. CONCLUSIONS: Our findings suggest that the low activity COMT genotype is protective against myocardial infarction. One may speculate that the altered estrogen status could be involved in this effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP-Hypertension-2.

OBJECTIVE: To perform a subgroup analysis on those patients in STOP-Hypertension-2 who had isolated systolic hypertension. DESIGN AND METHODS: The STOP-Hypertension-2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs (diuretics, beta-blockers) with that of newer ones [angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists]. In all, 6614 elderly patients with hypertension (mean age 76.0 years, range 70-84 years at baseline) were included in STOP-Hypertension-2. In the present subgroup analysis of STOP-Hypertension-2, isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg, in accordance with the Syst-Eur and Syst-China study criteria. In total, 2280 patients in STOP-Hypertension-2 met these criteria. In the study, patients were randomized to one of three treatment groups: "conventional" antihypertensive therapy with beta-blockers or diuretics (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or fixed-ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily); ACE inhibitors (enalapril 10 mg or lisinopril 10 mg daily); or calcium antagonists (felodipine 2.5 mg or isradipine 2.5 mg daily). Analysis was by intention to treat. RESULTS: The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens: 35/13 mmHg in the conventional group (n=717), 34/12 mmHg in the ACE inhibitor group (n = 724), and 35/13 mmHg in the calcium antagonist group (n=708). Prevention of cardiovascular mortality, the primary endpoint of the study, did not differ between the three treatment groups. All stroke events, i.e. fatal and non-fatal stroke together, were significantly reduced by 25% in the newer-drugs group compared with the conventional group (95% CI 0.58-0.97; p=0.027). This difference was attributable to reduction of non-fatal stroke while fatal stroke events did not differ between groups. New cases of atrial fibrillation were significantly increased by 43% (95% CI 1.02-1.99; p=0.037) on "newer" drugs compared with "conventional" therapy, mainly attributable to the calcium antagonists. There were no significant differences between the three treatment groups with respect to the risks of myocardial infarction, sudden death or congestive heart failure. CONCLUSIONS: The analysis demonstrated that "newer" therapy (ACE inhibitors/calcium antagonists) was significantly better (25%) than "conventional" (diuretics/beta-blockers) in preventing all stroke in elderly patients with isolated systolic hypertension.

Adrenergic beta-Antagonists↗
PubMed2004

Serum leptin and myocardial infarction in hypertension.

The adipose tissue-derived hormone leptin is among the physiologic processes involved in cardiovascular regulation. The aim of the present study was to elucidate if serum leptin may predict cardiovascular risk, particularly myocardial infarction (MI), in hypertensive men and women. In a prospective study cohort of hypertensive men and women, serum leptin was compared in 171 patients with MI and in 342 matched controls. The mean serum concentration of leptin was 25.1 +/- 20.0 ng/ml in the MI patients and 20.0 +/- 16.6 ng/ml in the controls (p = 0.007). The association between serum leptin and MI was independent of traditional risk factors. Leptin concentrations were higher in women than in men. In women, serum leptin was the most important predictor of MI. The present study indicates that serum leptin is associated with MI in a hypertensive population. Leptin concentrations may be of practical importance when estimating the risk of MI, especially in women, where leptin was found to be the most important predictor for MI.

Case-Control Studies↗
PubMed2004

Development of diabetes is retarded by ACE inhibition in hypertensive patients--a subanalysis of the Captopril Prevention Project (CAPPP).

OBJECTIVE: The Captopril Prevention Project (CAPPP) was designed as a prospective intervention trial comparing the effect of a treatment based on the angiotensin-converting enzyme (ACE) inhibitor captopril with that of a conventional diuretic and/or beta-blocker-based therapy, in 10,985 hypertensive patients. There was no difference in the primary cardiovascular morbidity and mortality endpoint. A lower incidence of diabetes mellitus during captopril treatment was observed in the whole CAPPP cohort that was non-diabetic at baseline (n = 10,413) as well as in such CAPPP patients that were previously untreated (n = 5033). METHODS AND RESULTS: A multivariate analysis of variables associated with the risk of developing diabetes in CAPPP demonstrated that glucose, body mass index (BMI), haemoglobin (Hb), age, 'SBP x Untreated' (the interaction between systolic blood pressure at baseline and newly diagnosed hypertension), cholesterol and prior antihypertensive treatment came out as risk factors. Based on these factors, a risk score for development of diabetes was calculated for all non-diabetic patients, who were divided into tertiles. For each tertile of risk, captopril therapy was associated with a reduced risk of diabetes development compared with conventional diuretic and/or beta-blocker therapy. When the non-diabetic cohort was divided into two subcohorts; previously treated and previously untreated patients, it turned out that the risk factors for developing diabetes differed between these two subcohorts. Only glucose, BMI and Hb came out as risk factors in all analysed cohorts. CONCLUSION: A captopril-based antihypertensive treatment regimen is associated with a lower risk of diabetes development, compared with conventional therapy based on diuretics and/or beta-blockers.

Adult↗