Search PubMed⌕ Search

Biomedical subjects

A Melander

Publications and source records attributed to A Melander.

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

Pharmacological intervention: the antidiabetic approach.

Impaired glucose tolerance (IGT) progresses to non-insulin-dependent diabetes mellitus (NIDDM) in many but not all IGT subjects. It remains unsettled whether long-term antidiabetic (i.e. antihyperglycaemic) pharmacotherapy delays the development of NIDDM, and whether such treatment influences macrovascular morbidity and mortality. This report summarizes the results from long-term (> 4 years) antihyperglycaemic interventions addressing these issues. In an American study, tolbutamide (0.5 g 2-3 times daily) promoted a 4-year improvement of glucose tolerance in young, non-obese, mildly diabetic asymptomatic subjects who apparently comprised a mixture of IGT and NIDDM. In a Swedish 5-year study on 178 survivors of myocardial infarction, of whom 79 had intravenous IGT, tolbutamide treatment was associated with improved glucose tolerance, reduced triglyceride levels, and improved 18-month survival. A British 5-year study on a subgroup of about 200 middle-aged men from the Whitehall cohort indicated that phenformin (50 mg once daily) did not influence the deterioration of glucose levels. In a 10-year British study, 241 middle-aged men and women were 4-square randomized to control, weight reduction, placebo and tolbutamide (0.5 g twice daily). A non-lasting reduction of arterial disease was recorded in those on tolbutamide. No reduction of NIDDM development was seen. In a Swedish 10-year study on middle-aged men with IGT, follow-up comprised 59 controls, 98 on diet advice with or without placebo, and 23 on tolbutamide (0.5 g three times daily) added to diet advice. A total of 29% developed NIDDM among controls and 13% in the diet group. In contrast, no subject maintaining tolbutamide treatment developed NIDDM. Moreover, the tolbutamide-treated subjects had reduced blood pressure, triglyceride and cholesterol levels, as well as fewer macrovascular complications. Recently, a lower mortality rate at 22 years after the start of tolbutamide treatment has been recorded. To summarize, treatment with insulin-releasing drugs might help to reduce the development of NIDDM and macrovascular disease in IGT subjects. However, further studies are needed to verify or refute this notion.

Controlled Clinical Trials as Topic↗
PubMed1998

Risk factor clustering in patients with hypertension and non-insulin-dependent diabetes mellitus. The Skaraborg Hypertension Project.

OBJECTIVES: To assess the coexistence of hypertension and diabetes, associations with cardiovascular risk factors and the achievement of current treatment goals. DESIGN: A community-based, cross-sectional, observational study. SETTING: Hypertension and diabetes outpatient clinics in primary health care, Skara, Sweden. SUBJECTS: All patients (n = 1116; 488 men, 628 women) who performed an annual follow-up from May 1992 to September 1993. MAIN OUTCOME MEASURES: Hypertension, non-insulin-dependent diabetes mellitus (NIDDM), blood pressure, fasting B-glucose, lipids, HbAlc, body mass index (BMI), waist hip ratio (WHR). RESULTS: Hypertension alone was found in 286 men and 430 women, hypertension and NIDDM combined in 102 men and 102 women, and NIDDM alone in 100 men and 96 women. Taking new cases into account, the proportion of hypertension among NIDDM patients was 57%, and the proportion of NIDDM among hypertensives was 26%. Men and women with both hypertension and NIDDM had a higher systolic blood pressure and women also had a higher diastolic blood pressure (men 168/88 mmHg, women 165/86 mmHg) than those with hypertension alone (men 152/87 mmHg, women 156/82 mmHg) (P < or = 0.001). Cardiovascular risk factors accumulated in patients with both hypertension and NIDDM (triglycerides, BMI and WHR). A diastolic blood pressure < or = 90 mmHg was achieved by 71% men and 84% women with hypertension. HbAlc < 7.5% was attained by 71% men and 70% women with NIDDM. CONCLUSIONS: A considerable coexistence of hypertension and NIDDM was demonstrated. Cardiovascular risk factors clustered in patients with both diseases and their blood pressure was less controlled. These patients thus comprised a clinically defined group at high risk. By current guidelines, control of hypertension and NIDDM seemed appropriate.

Cluster Analysis↗
PubMed1998

Prolonged elimination of tolbutamide in a premature newborn with hyperinsulinaemic hypoglycaemia.

So far, gestational diabetes treated with tolbutamide has never been associated with severe hypoglycaemia in the newborn when the mother's diabetes was well controlled. We report a case of a premature neonate, gestational age 34 weeks, with severe and long-standing hypoglycaemia from birth. The mother had well-controlled gestational diabetes, treated with tolbutamide from the 24th week of gestation until delivery. The neonate had inappropriately high levels of serum proinsulin, insulin and C-peptide relative to blood glucose concentrations. From day 19 after birth, the levels were normalized. Serum tolbutamide was 140.6 micromol/l (38 microg/ml) at 3 h after birth. Zero-order kinetics were seen during the first 90 postnatal hours. The half-life of serum tolbutamide decreased from 46 to 6 h. It is suggested that tolbutamide, when given to the mother until delivery, may cause severe and prolonged hyperinsulinaemic hypoglycaemia in premature neonates. The initially prolonged tolbutamide half-lives and zero-order kinetics suggest immaturity of hepatic elimination during the first 2 days of postnatal life.

Adult↗
PubMed1998

Is there a concentration-effect relationship for sulphonylureas?

Sulphonylureas have remained the mainstay of oral therapy for type 2 (non-insulin-dependent) diabetes mellitus (NIDDM). They stimulate insulin release from pancreatic beta cells. Pharmacokinetic differences between the various sulphonylureas are of clinical importance in terms of the time to onset of action, timing of drug administration in relation to food intake, magnitude and duration of the glucose-lowering effect and the risk of serious hypoglycaemia. Recent studies with improved analytical sensitivity have shown that the elimination half-life of glibenclamide is longer than previously thought and that 2 metabolites of glibenclamide have significant hypoglycaemic activity. Furthermore, single dose studies in healthy volunteers using an integrated pharmacokinetic-pharmacodynamic model have identified clear concentration-effect relationships for both glibenclamide and its metabolites after oral and intravenous administration. Under multiple dose conditions, kinetic-dynamic relations have been identified with shorter-acting drugs in dosages that give discontinuous sulphonylurea exposure. However, at continuous exposure, i.e. sustained 24-hour therapeutic concentrations in plasma, there is evidence indicating the development of tolerance, which may be caused by downregulation of beta cell sensitivity. As more sophisticated concentration-effect studies appear, it has become evident that currently recommended maximum daily doses of many sulphonylureas are too high.

Diabetes Mellitus, Type 2↗
PubMed1997

Glucose tolerance and mortality, including a substudy of tolbutamide treatment.

Mortality according to glucose tolerance was studied to determine the prognosis of impaired glucose tolerance. Among 2500 persons tested in a community screening programme in 1962-1965 and followed-up for mortality to the end of 1987, age-sex-adjusted mortality rates were 37.9 +/- 1.9, 53.6 +/- 4.2, and 70.1 +/- 3.6 deaths per 1000 person-years (+/-SE) in those with normal glucose tolerance, impaired glucose tolerance, and diabetes by World Health Organization criteria at baseline. Age-sex-adjusted mortality rates due to ischaemic heart disease were 14.3 +/- 1.1, 16.3 +/- 2.4, and 25.8 +/- 2.0 deaths per 1000 person-years, respectively. Using criteria predating those of the World Health Organization 147 men with abnormal glucose tolerance were entered into a randomized clinical trial in which 49 were treated with tolbutamide for approximately 10 years. Those treated had lower mortality rates from all causes (mortality rate ratio = 0.66, 95% confidence interval = 0.39, 1.10) and from ischaemic heart disease (mortality rate ratio = 0.42, 95% confidence interval = 0.16, 1.12) than those not receiving tolbutamide. Thus mortality rates are increased in persons with impaired glucose tolerance and diabetes, and the small clinical trial suggests that tolbutamide may be beneficial in men with abnormal glucose tolerance.

Adolescent↗
PubMed1997

Concentration-effect relations of glibenclamide and its active metabolites in man: modelling of pharmacokinetics and pharmacodynamics.

AIMS: The main purpose of this paper is to describe the relationship between serum concentrations of glibenclamide and its main metabolites and the effects on blood glucose levels, the clinically most relevant parameter to assess in diabetes. METHODS: Serum concentrations and blood glucose lowering effects (expressed as percent blood glucose reduction vs placebo) of glibenclamide (Gb) and its active metabolites, 4-trans-hydroxy-(M1) and 3-cis-hydroxy-glibenclamide (M2), were analysed in eight healthy subjects participating in a placebo-controlled, randomized, single-blind crossover study, using intravenous administration of each compound as well as oral administration of Gb. RESULTS: Plots of % blood glucose reduction vs log serum concentration demonstrated counter-clockwise hysteresis for parent drug and its metabolites. An effect compartment was linked to appropriate pharmacokinetic models and pharmacokinetic and pharmacodynamic modelling was used to fit the pharmacokinetics of Gb by both routes and the metabolites for each individual. Based on the individual concentration-time profiles a PK/PD-model was applied to all effect data simultaneously. An increase in the steady-state serum concentration when the effect is 50% of maximal, CEss50, was found in the sequence M1 (23 ng ml-1), M2 (37 ng ml-1) and Gb (108 ng ml-1). Corresponding interindividual variabilities expressed as CV% were 25%, 47% and 26%. The elimination rate constants from the effect site (kEO) were estimated and increased in the order M1 (0.178 h-1, CV 13%), M2 (0.479 h-1, CV 8.5%) and Gb (1.59 h-1, CV 36%). Corresponding equilibration half-lives for the effect site (kEO-HL) were 3.9 h, 1.4 h and 0.44 h. Estimated Emax-values obtained for M1, M2 and Gb were 40% (CV 30%), 27% (CV 56%) and 56% (CV 14%), respectively. CONCLUSIONS: It is concluded that the two major metabolites of Gb are hypoglycaemic in man, that they may have higher activity at low concentrations and that they may have a longer effect duration than the parent drug.

Adult↗
PubMed1996

Incidence of myocardial infarction in elderly men being treated with antihypertensive drugs: population based cohort study.

OBJECTIVE: To analyse the association between use of antihypertensive treatment, diastolic blood pressure, and long term incidence of ischaemic cardiac events in elderly men. DESIGN: Population based cohort study. Baseline examination in 1982-3 and follow up for up to 10 years. SETTING: Malmŏ, Sweden. SUBJECTS: 484 randomly selected men born in 1914 and living in Malmŏ during 1982. MAIN OUTCOME MEASURES: Observational comparisons of incidence rates and rate and hazard ratios of ischaemic cardiac events (myocardial infarction or death due to chronic ischaemic cardiac disease). RESULTS: The crude incidence rate of ischaemic cardiac events was higher in those subjects who were taking antihypertensive drugs than in those who were not (rate ratio 2.6 (95% confidence interval 1.7 to 3.9)). After adjustment for potential confounders (differences in baseline smoking habits, blood pressure, time since diagnosis of hypertension, ischaemic or other cardiovascular disease, hypercholesterolaemia, hypertriglyceridaemia, diabetes mellitus, obesity, and raised serum creatinine concentration) this rate was reduced but still raised (hazard ratio 1.9 (1.0 to 3.7)). In men with diastolic blood pressure > 90 mm Hg, antihypertensive treatment was associated with a twofold increase in the incidence of ischaemic cardiac events (rate ratio 2.0 (1.1 to 3.6)), which vanished after adjustment for potential confounders (hazard ratio 1.1 (0.5 to 2.6)). In those subjects with diastolic blood pressure < or = 90 mm Hg, antihypertensive treatment was associated with fourfold increase in incidence (rate ratio 3.9 (2.1 to 7.1)), which remained after adjustment for potential confounders (hazard ratio 3.8 (1.3 to 11.0)). CONCLUSION: Antihypertensive treatment may increase the risk of myocardial infarction in elderly men with treated diastolic blood pressures < or = 90 mm Hg.

Aged↗
PubMed1996

Increased risk of ischaemic heart disease mortality in elderly men using anxiolytics-hypnotics and analgesics. Results of the 10-year follow-up of the prospective population study "Men born in 1914", Malmo, Sweden.

OBJECTIVES: An increased risk of all-cause and cardiovascular mortality in users of anxiolytic-hypnotic drugs (AHD) has been reported, and use of analgesics may be an additional factor. Therefore, we examined the association of AHD and analgesic use, alone and in combination, with all-cause and ischaemic heart disease (IHD) mortality. METHODS: Multivariate 10-year survival analysis in a population based cohort of 500 men born in 1914. Relative risks (RR) were adjusted by relevant confounders (blood pressure, serum cholesterol, diabetes mellitus, smoking habit, high alcohol consumption, history of previous IHD, cancer, and other diseases). RESULTS: The RR of both all-cause and IHD mortality were significantly increased among those using both AHD and analgesics compared to those who took neither of these drugs: RR = 1.8 for all-cause mortality, and RR = 2.7 for IHD mortality. CONCLUSION: Although the number of cases was small, warranting interpretative caution, the current study suggests that the combined use of AHD (mainly benzodiazepines) and analgesics seems to be associated with an increase in all-cause and IHD mortality in elderly men.

Aged↗
PubMed1996

Comparison of dose standard units for drug utilisation studies.

OBJECTIVE: As employment of different dose standards would be impractical and confusing, the aim of this article is to compare the define daily dose (DDD) with some more recently proposed standards, namely, the minimum marketed dose (MMD), the equipotential dose (ED), the average daily dose (ADD), and the non-standard prescribed daily dose (PDD). METHODS: Literature review, critical comparative analysis. RESULTS: The DDD, defined by an independent scientific committee assisting the WHO Collaborating Centre for Drugs Statistics Methodology, has been employed in a large number of national and international comparative studies at the population level, usually as number of DDDs per 1000 inhabitants per day. However, the DDD can also be used at the individual level. The PDD, not being a standard unit, can be appropriately used in a second step to explain differences detected by the DDD methodology. CONCLUSIONS: A globally accepted dose standard unit is important in drug utilisation studies, particularly if different investigations are to be compared. None of the alternatives seemed to offer any advantage over the DDD. Hence there is reason to advocate use of the DDD as the sole standard dose unit in all pharmacoepidemiologic studies.

Drug Utilization↗
PubMed1996

Postural and symptomatic improvement after physiotherapy in patients with dizziness of suspected cervical origin.

OBJECTIVE: To assess postural performance in patients with dizziness of suspected cervical origin in whom extracervical causes had been excluded, and to assess the effects of physiotherapy on postural performance and subjective complaints of neck pain and dizziness. DESIGN: Prospective, randomized, controlled trial. SETTING: Primary care centers and a tertiary referral center. PATIENTS AND SUBJECTS: Of 65 referrals, 43 patients were excluded because extracervical etiology was suspected. Of the remaining 22 patients, 17 completed the study (15 women, 2 men, x age 37 yr, range 26-49). The controls were 17 healthy subjects (15 women, 2 men, x age 36 yr, range 25-55). INTERVENTION: Physiotherapy based on analysis of symptoms and findings, and aimed to reduce cervical discomfort. Patients were randomized either to receive immediate physiotherapy (n = 9), or to wait 2 months, undergo repeat measurements, and then receive physiotherapy (n = 8). MAIN OUTCOME MEASURES: Posturography, measuring velocity and variance of vibration-induced body sway and variance of galvanically induced body sway. Subjective intensity of neck pain (Visual Analog Scale ratings, 0-100), intensity and frequency of dizziness (subjective score 0-4). RESULTS: The patients manifested significantly poorer postural performance than did healthy subjects (.05 > p > .0001). Physiotherapy significantly reduced neck pain and intensity and the frequency of dizziness (p < .01), and significantly improved postural performance (.05 > p > .0007). CONCLUSIONS: Patients with dizziness of suspected cervical origin are characterized by impaired postural performance. Physiotherapy reduces neck pain and dizziness and improves postural performance. Neck disorders should be considered when assessing patients complaining of dizziness, but alternative diagnoses are common.

Adult↗
PubMed1996

Body mass index and disability pension in middle-aged men--non-linear relations.

BACKGROUND: Obesity has, in a number of studies, been found to correlate to disability and mortality, primarily due to diseases of the circulatory and musculoskeletal systems. In addition, an excess mortality among underweight subjects has been observed in previous studies. METHODS: Five complete birth-year cohorts (1926-1930) of male residents in Malmö (n = 7697) were invited to the survey at the Department of Preventive Medicine, Malmö General Hospital, and 5926 (77%) attended with complete data. Each subject was followed from inclusion, defined by the date of examination, until the end of the calendar year when he turned 58, a total study period of approximately 11 years. Data on about 300 questionnaire items and laboratory tests were determined at the health survey visit. Nationwide Swedish data registers were used for surveillance. RESULTS: Of the participants, 4.7% were underweight, 37.7% overweight, 7.3% obese and 50.3% normal weight; 849 (14.3%) had been granted disability pension at the end of follow-up, 717 after screening. After adjustment for smoking there was a J-shaped relation between body mass index (BMI) and incidence of disability pension, the relative risk ( with the normal group as reference) among underweight men being 1.9. For the overweight subjects it was 1.3 and for the obese 2.8, all differences were significant. Disease of the musculoskeletal and circulatory systems and mental disorders accounted for 67.2% of all main diagnoses resulting in disability pensions during follow-up. A total of 377 (6.4%) men died during follow-up. Diseases of the circulatory system, neoplasms, injury/poisoning and diseases of the respiratory system accounted for 91.8% of the deaths. CONCLUSIONS: Both underweight, overweight and obesity were related to risk of disability pension, with a J-shaped risk relationship.

Body Mass Index↗
PubMed1996

Review of previous impaired glucose tolerance intervention studies.

Long-term intervention studies have evaluated the effect of diet, exercise and pharmacological regimens on the conversion rate of impaired glucose tolerance (IGT) to non-insulin dependent diabetes mellitus (NIDDM). Two UK studies, the Bedford study (10 years) and the Whitehall study (5 years), found that a diet which restricts carbohydrate intake to less than 120 g/day had no effect on the development of NIDDM in subjects with IGT. In contrast, the Swedish Malmöhus study (10 years) found that the conversion rate was reduced from 29% in the control group to 13% in a group told to limit their intake of carbohydrates and lipids and to reduce weight when overweight. A further Swedish study, the Malmö study (6 years and ongoing) is investigating a combination of dietary intervention and a strenuous exercise programme. In this study the conversion rate decreased from 29% in the control group to 11% in the diet plus exercise group. The Bedford and Whitehall studies also investigated intervention with tolbutamide and phenformin, respectively. Neither drug was found to have an effect on the conversion rate in either study. In contrast, positive results for tolbutamide were obtained in the Malmöhus study. No subjects in the tolbutamide plus diet group developed NIDDM compared with 29% in the control group. This regimen was also found to have beneficial effects on blood pressure, serum lipids and on cardiovascular morbidity and mortality.

Diabetes Mellitus, Type 2↗
PubMed1996

Oral antidiabetic drugs: an overview.

Chronic hyperglycaemia, i.e. impaired glucose tolerance (IGT) and NIDDM, conveys a great risk of macrovascular disease. Both insulin resistance and impaired insulin secretion seem necessary to establish chronic hyperglycaemia, and untreated it appears to promote and worsen both insulin resistance and impaired insulin secretion. The prevention and treatment of chronic hyperglycaemia should include measures directed at both derangements, and the therapeutic goal should be normoglycaemia. As this is rarely achieved by non-pharmacologic treatment alone, addition of oral antidiabetic drugs are often indicated. Their ability to attain euglycaemia is greater the earlier they are employed, but they should never be introduced until after optimization of non-pharmacologic measures. Delayed early insulin response to glucose or a meal always accompanies chronic hyperglycaemia and is not normalized by non-pharmacologic treatment. This justifies the use of insulin-releasing drugs with a rapid onset of action, e.g. the sulphonylurea glipizide. The non-sulphonylureas, repaglinide and A-4166, are even more rapid- and also short-acting, representing a reduced risk of long-lasting, and hence dangerous, hypoglycaemia. Continuous exposure to high concentrations of sulphonylureas may downregulate beta-cell sensitivity. Maximum doses are much lower than previously assumed. The most effective improvers of insulin action seem to be the thiazolidinediones, but they are not yet marketed. Metformin is the only globally available drug for improving insulin action. It is as antihyperglycaemic as sulphonylureas but does not cause hyperinsulinaemia, weight increase or hypoglycaemia. The risk of lactic acidosis can be minimized by avoiding metformin in subjects with renal impairment. Combined treatment with sulphonylurea and metformin can be highly effective even in advanced NIDDM.

Biguanides↗
PubMed1995

Pharmacokinetic interactions of alcohol and acetylsalicylic acid.

This study assessed the influence of acetylsalicylic acid (ASA, 1.0 g), ibuprofen (0.8 g) and paracetamol (1.0 g) on the single-dose kinetics of ethanol in 12 healthy volunteers ingesting the drug and a standardised 1840-kJ breakfast 1 h before intake of ethanol. It also assessed the influence of ethanol on the single-dose kinetics of 1.0 g ASA in ten fasting healthy volunteers. Plasma concentrations of ethanol were measured by gas chromatography, and those of the drugs by liquid chromatography. There was no effect of ASA, ibuprofen or paracetamol on the single-dose kinetics of ethanol, but concurrent intake of ethanol reduced the peak concentration of ASA by 25%.

Acetaminophen↗