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Biomedical subjects

R Sannerstedt

Publications and source records attributed to R Sannerstedt.

At least 19 recordsLinked to original sources

Drugs during pregnancy: an issue of risk classification and information to prescribers.

The Swedish system for the classification of fetal risk of drugs was the first of its kind and was implemented in 1978. Drugs for use in pregnant women are classified in 4 general categories--A to D. The US Food and Drug Administration (FDA) introduced a system in 1979 also using the letters A to D, together with an X category. However, the definitions differ considerably between the FDA system and the Swedish system, resulting in a very different allocation of drugs to the respective categories. In the Swedish system, category A includes drugs that have been extensively used and/or for which there are reliable clinical data indicating no evidence of disturbance of the reproductive process. Category B includes drugs for which data from pregnant women are insufficient for making any solid estimation of human teratogenic risk, and classification is therefore based on animal data, with allocation to 3 subgroups. For products in category C, the pharmacological action of the drug may have undesirable effects on the human fetus or newborn infant. Finally, category D contains drugs for which human data indicate an increased incidence of malformations. The categorisation statement is always followed by a short explanatory text. In contrast to the FDA system, the Swedish system has been well accepted, as judged by an interview study including 934 physicians and pharmacists. We believe that much of the American dissatisfaction may be a consequence of shortcomings in the category definitions of the FDA system. The FDA system requires an unrealistically high quality of data, e.g. the availability of controlled studies in pregnant women that fail to demonstrate a risk to the fetus are needed for a drug to be assigned to category A. Consequently, the majority of drugs on the US market are allocated to category C, interpreted as 'risk cannot be ruled out'. The distribution of drugs into the various categories is thus very different between the Swedish and FDA systems. We think that the issue of this debate reflects a fundamental problem related to public health information: how should a large, compounded, changing and difficult to evaluate databank be organised before it is made available to professionals and secondarily to lay people?

Australia↗

Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels.

Twenty-three healthy men (age 25 to 50 years), covering a wide range of fatness and body fat distribution, were studied. An oral glucose tolerance test was performed and adipose tissue areas were calculated from computed tomography (CT) scans made at the level of L4/L5. Visceral fat area was associated with elevated concentrations of insulin and C-peptide and with glucose intolerance before and after the oral glucose load. Concentrations of sex-hormone-binding globulin (SHBG), as well as total and free testosterone, were negatively correlated with waist/hip circumference ratio and visceral fat area and also negatively associated with increased glucose, insulin, and C-peptide concentrations. In multiple linear regression, adjusting for age, body mass index, and visceral fat area, serum concentrations of free testosterone were still negatively correlated with glucose, insulin, and C-peptide levels. Without claiming any causality in the observed associations, we conclude that, unlike in women, abdominal fat distribution, insulin, glucose, and C-peptide levels are negatively associated with serum testosterone levels in men.

Adipose Tissue↗

Does hyperkinetic circulation constitute a pre-hypertensive stage? A 5-year follow-up of haemodynamics in young men with mild blood pressure elevation.

In a previous haemodynamic examination, 44 young men (18-22 years) with blood pressure elevation above the 98th percentile, mean arterial blood pressure (MAP) greater than or equal to 95 +/- 6 mm Hg, showed an increased cardiac index (dye-dilution) and an enhanced resistance at maximal vasodilation of the hand (venous occlusion plethysmography during hyperaemia). This latter finding suggested arteriolar wall hypertrophy. However, the subgroup with the highest cardiac index (greater than or equal to 3.86 1 min-1 x m2) (n = 18) displayed normal vascular resistance at maximal dilation in comparison with the normotensive control group (n = 29). Consequently, functional signs of arteriolar hypertrophy were restricted to individuals with normal or low cardiac index. At the re-investigation 5 years later, a significant reduction in blood pressure was observed in the normotensive control group (MAP: from 88 +/- 7 to 85 +/- 7 mm Hg, P less than 0.05). There was no change in individuals with initially elevated blood pressure. Furthermore, cardiac index fell significantly with time in this latter group. Thus, the blood pressure elevation in the hypertensive group, previously mainly dependent on high blood flow was, 5 years later, more related to an increased total peripheral resistance, (delta total peripheral resistance = 8%). However, no definite evidence indicating development of hypertrophy of the resistance vessels of the hand was observed during the follow-up period. Since the hyperkinetic subgroup did not display a concomitant fall in blood pressure with cardiac output, our results do not support the theory that the hyperkinetic form of borderline hypertension is a temporary phenomenon, explained by the inclusion of anxious individuals afraid of the experimental situation. Hyperkinetic hypertension may be the initial phase of sustained hypertension in a subgroup of the future hypertensive population.

Adult↗

Regional distribution of muscle and fat mass in men--new insight into the risk of abdominal obesity using computed tomography.

We studied 24 healthy men (25-50 years old) covering a wide range of fatness (body mass index range: 21-34 kg/m2) and fat distribution (waist/hip range: 0.75-1.06). Computed tomography scans were taken at five levels (thigh, hip, waist, arm, and liver) from which fat, muscle and bone areas were calculated. Both waist/hip and BMI were correlated with fat areas in the thigh, arm and waist scans. BMI showed stronger correlations with peripheral fat areas, whereas waist/hip showed stronger correlations with fat areas in the waist scan (particularly with visceral fat area: r = 0.88, P less than 0.001). BMI was correlated with muscle and bone areas in the thigh scan. In multiple regression BMI was, independently of waist/hip and age, positively correlated with fat areas in the arm, thigh, and waist (not with visceral fat) and muscle and bone areas in the thigh. Waist/hip was independently of BMI and age correlated with fat areas in the arm and waist, including visceral fat area (but not with fat areas in the thigh). Moreover, waist/hip showed an independent negative correlation with muscle area in the thigh, muscle endurance and physical activity. Serum triglycerides, plasma insulin, glucose, uric acid and diastolic and systolic blood pressure were associated with visceral fat area but also to anthropometric indicators of abdominal fat distribution (especially waist/hip ratio). Liver attenuation, but not the liver/spleen attenuation ratio, was associated with some liver enzymes and BMI but not with waist/hip or metabolic parameters. We conclude that a higher BMI is associated with increased central and peripheral fat stores (but not visceral fat) and increased thigh muscle whereas waist/hip is primarily associated with increased central fat stores (noteably with visceral fat), decreased thigh muscle and reduced physical fitness. It is suggested that physical training might be an important element in the treatment of abdominal obesity in men.

Abdomen↗

Blood pressure response in relation to blood lactate during exercise in patients with essential hypertension.

Thirty-four untreated patients with essential hypertension WHO I-II, 17 patients under treatment with beta-blockade, and 32 healthy controls with a wide range of exercise capacity were studied at loadless pedaling (W0) and at the work load eliciting a blood lactate concentration corresponding to 4 mmol X l-1 (onset of blood lactate accumulation or OBLA). At W0 the treated patients had approximately the same systolic blood pressure (SBP) as the healthy controls, while the untreated patients had a higher SBP than the controls. At WOBLA the SBP was higher in the untreated patients than in both the treated patients and the healthy controls. On an individual basis it was found in the healthy controls and the untreated patients that the SBP at WOBLA showed a slight and insignificant increase versus SBP at W0, whereas the difference in SBP between WOBLA and W0 ("exercise SBP increase") demonstrated an inverse relationship (P less than 0.001-0,01) versus W0. It was suggested that for both healthy controls and untreated patients the exercise SBP depended on a "basal" level as depicted by W0 and a further SBP increase due to the exercise load. The difference between the two groups was that the patients with untreated hypertension displayed their relationships at higher pressure levels indicating the presence of a hyperkinetic drive. The treated patients appeared to have a lower increase in SBP between W0 and WOBLA than any other group, suggesting an unfavorable effect of the beta-blockade.

Adrenergic beta-Antagonists↗

Drug use during pregnancy and breast-feeding. A classification system for drug information.

Since 1978 the Swedish catalogue of registered pharmaceutical specialties (FASS) has carried a special section entitled "Pregnancy and breast-feeding" in each product presentation, intended to form an aid for the prescription of drugs to women during childbearing and lactation. After a brief review of transplacental transport and milk secretion, reproduction-toxicology studies in animals, and methods for clinical evaluation of drugs for use during pregnancy, the classification system is presented. On the basis of available data with regard to effects on early and late stages of pregnancy and labour, all the pharmaceutical specialties concerned are assigned to one of the following pregnancy categories: A, B 1, B 2, B 3, C or D. The letters refer to information based on findings in man, and the figures to information based on animal data. For drugs in categories B 3, C or D any harmful effects observed or likely to occur in man or animals are to be specified. The pregnancy categories are defined as follows: Category A. Drugs which may be assumed to have been used by a large number of pregnant women and women of child-bearing age, without any form of definite disturbance in the reproductive process having been noted so far, e.g. an increased incidence of malformations or other direct or indirect harmful effects on the fetus. Category B. Drugs which may be assumed to have been used by only a limited number of pregnant women and women of child-bearing age, without any form of definite disturbance in the reproduction process having been noted so far, e.g. an increased incidence of malformations or other direct or indirect harmful effects on the fetus. Category C. Drugs which by their pharmacological effects have caused, or must be suspected of causing disturbances in the reproduction process that may involve risk to the fetus without being directly teratogenic. Category D. Drugs which have caused an increased incidence of fetal malformations or other permanent damage in man or which on the basis of e.g. reproduction-toxicology studies must be suspected of doing so. This category comprises drugs with primary teratogenic effects. If the drug also has pharmacological effects that may directly or indirectly have a harmful effect on the fetus, this must also be stated. As experience of effects of drugs in Category B is limited, results of reproduction-toxicology studies in animals are indicated by allocation to one of three subgroups according to the following definitions: Category B 1.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗

Essential hypertension--implications for pathogenesis from repeated haemodynamic investigations in young men with elevated blood pressure.

Repeated invasive haemodynamic studies were performed in young men (18-21 years) with elevated blood pressures and age and sex-matched normotensive controls before military service and five years later as a follow-up study. Patients with high blood pressure initially showed increased cardiac output and increased vascular resistance during maximal vasodilatation. The latter observation suggests arteriolar wall hypertrophy but was restricted to the subgroup of patients with low/normal cardiac output (normokinetic subgroup). In the follow-up study the cardiac output in patients with high blood pressure was no longer increased in comparison with controls and this normalization was restricted to patients previously showing the highest cardiac output (hyperkinetic subgroup). Contrary to the hypothesis this subgroup of patients had not developed significant signs of arteriolar wall hypertrophy although a tendency was present.

Adult↗

Blood pressure and heart rate recordings at home and at the clinic. Evidence for increased cardiovascular reactivity in young men with mild blood pressure elevation.

In 41 apparently healthy men, aged 22-25 years, with mild blood pressure elevation (MBPE) and 19 age- and sex-matched normotensive controls (MC), blood pressure (BP) and heart rate (HR) readings at the clinic were compared to self-determined morning and afternoon values at home. The criteria for inclusion in the MBPE group were auscultatory BP less than 150 mmHg systolic and/or less than 90 mmHg diastolic at the military enlistment center from which the subjects were recruited, and systolic BP less than 140 mmHg on two subsequent occasions at the clinic. The BPs of the controls, who were mainly recruited from the same center, did not exceed 130/80 mmHg either at the enlistment center or at the clinic. The magnitude of the difference in systolic BP between home and clinic readings in the MBPE group (+15.3 mmHg) differed significantly from that in the NC group (+1.8 mmHg) (p less than 0.001). In both groups the systolic BP increased slightly but significantly during the day and was higher at home in the afternoon than in the morning. HR showed the same type of variation as BP in both groups with higher values at the clinic. The rise tended to be more pronounced (p less than 0.1) in patients with MBPE. Surprisingly, resting HR at home in the morning was significantly lower in the MBPE than in the NC group. Normokinetic and hyperkinetic subgroups of patients with MBPE did not differ from each other with respect to the variations in HR and BP studied.

Adult↗

Medication during pregnancy and breast-feeding--a new Swedish system for classifying drugs.

As an aid for the prescription of drugs for women during pregnancy and lactation, a special section entitled "Pregnancy and breast-feeding" has been added to the description of most of the products in the Swedish catalogue of registered pharmaceutical specialties (FASS) since 1978. This article describes the system and also presents examples of the general texts proposed for certain groups of drugs.

Breast Feeding↗

Effect of treatment of hypertension in the primary preventive trial, Göteborg, Sweden.

1 A treatment group comprising 635 hypertensive men (casual SBP greater than 175 or DBP greater than 115 twice) was compared with a reference group (n = 391 men; casual SBP greater than 175 or DBP greater than 115 only at screening). All men belonged to the same population sample of 7,455 men aged 47-54 yr. 2 The two groups did not differ with respect to age, smoking habits or cholesterol values, but screening BPs were higher in the treatment group. 3 During 4.3 years' follow-up there was a significantly lower total death rate in the treatment group compared with reference group. 4 There was also a strong tendency towards lower incidence of non-fatal myocardial infarction (P = 0.06). The pooled incidence of non-fatal myocardial infarction and fatal CHD was lower in the treatment group than in the reference group (P less than 0.03).

Adrenergic beta-Antagonists↗

Coronary heart-disease after treatment of hypertension.

Within a group of 1026 men aged 47-54, cause-specific death-rates and the incidence of non-fatal myocardial infarction and stroke in treatment group of 635 hypertensive men (casual systolic B.P. greater than 175 or diastolic B.P. greater than 115 mm Hg on two occasions) treated at a hypertension clinic were compared with those in a control group of 391 men (causal systolic B.P. greater than 175 or diastolic greater than 115 mm Hg on only one occasion) who remained mainly untreated during their 4.3 years of follow-up. The predicted risk of coronary heart-disease (C.H.D.) at entry, calculated by a multiple logistic function, was slightly higher in the treatment group. Total death-rate during follow-up was significantly lower in the treatment group (3.3%) than in the control group (6.1%). The difference in death-rate for C.H.D. was of the same relative order (0.8% versus 1.5%), as was the incidence of non-fatal myocardial infarction (2.8% versus 5.4%), although none of the differences reached statistical significance. However, the pooled incidence of fatal and non-fatal C.H.D. was significantly lower in the treatment group (3.6%) than in the control group (6.9%). The results suggest that antihypertensive treatment might be effective in preventing or postponing C.H.D. in middle-aged men.

Cerebrovascular Disorders↗

Haemodynamic effects of static and dynamic exercise in males with arterial hypertension of varying severity.

Sustained handgrip at 30% of the maximal strength and submaximal supine bicycle exercise elicited mean blood pressure increases of similar magnitude in healthy males and in men with essential hypertension WHO Stage 1 and 2, but with different contributions of systolic and diastolic blood pressure changes. While systolic blood pressure exceeded 22.7 kPa (170 mmHg) during static exercise in every hypertensive man, this did not occur in any of the control subjects. During dynamic exercise, the arterial blood pressure increase per litre increase in cardiac output was significantly less than during static exercise, indicating different patterns of circulatory adaptation to these two forms of stress. Combination of dynamic and static exercise tests might be of value for identifying subjects with a hypertensive pattern of circulatory regulation.

Blood Pressure↗