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Biomedical subjects

L Lind

Publications and source records attributed to L Lind.

At least 109 records · Page 6Linked to original sources

Atrial fibrillation is an independent determinant of low cognitive function: a cross-sectional study in elderly men.

BACKGROUND AND PURPOSE: Cerebrovascular disease is increasingly recognized as a cause of dementia and cognitive decline. We have previously reported an association between hypertension and diabetes and low cognitive function in the elderly. Atrial fibrillation is another main risk factor for cerebrovascular disease. The aim of this study was to investigate whether atrial fibrillation is associated with low cognitive function in elderly men with and without previous manifest stroke. METHODS: This was a cross-sectional study based on a cohort of 952 community-living men, aged 69 to 75 years, in Uppsala, Sweden. Cognitive functions were assessed by the Mini-Mental State Examination and the Trail Making Tests, and a composite z score was calculated. The relation between atrial fibrillation and cognitive z score was analyzed, with stroke and other vascular risk factors taken into account. RESULTS: All analyses were adjusted for age, education, and occupational level. Men with atrial fibrillation (n=44) had lower mean adjusted cognitive z scores (-0.26+/-0.11) than men without atrial fibrillation (+0.14+/-0.03; P=0.0003). The exclusion of stroke patients did not alter this relationship; the mean cognitive z score was -0.24+/-0.12 in the 36 men with atrial fibrillation and +0.17+/-0.03 in those without atrial fibrillation (P=0.0004), corresponding to a difference of 0.4 SDs between groups. Adjustments for 24-hour diastolic blood pressure and heart rate, diabetes, and ejection fraction did not change this relationship. Men with atrial fibrillation who were treated with digoxin (n=27) performed markedly better (-0.05+/-0.21) than those without treatment (n=9; -1.14+/-0.34; adjusted P=0.0005). Previous myocardial infarction was not associated with impaired cognitive results. CONCLUSIONS: In these community-living elderly men, we found an association between atrial fibrillation and low cognitive function independent of stroke, high blood pressure, and diabetes. Interventional studies are needed to answer the question of whether optimal treatment of atrial fibrillation may prevent or postpone cognitive decline and dementia.

Aged↗

Effect of physiological hyperinsulinemia on blood flow and interstitial glucose concentration in human skeletal muscle and adipose tissue studied by microdialysis.

The effect of an euglycemic-hyperinsulinemic glucose clamp (94 +/- 5 microU/ml) on blood flow and glucose extraction fraction in human skeletal muscle and adipose tissue was investigated. Limb blood flow was measured by venous occlusion pletysmography and tissue blood flow by the microdialysis ethanol technique. Insulin infusion resulted in an increased blood flow in the calf and forearm (64 and 36%, respectively; P < 0.01) but not in the studied muscles of these limbs (ethanol outflow-to-inflow ratio: m. gastrocnemius 0.144 +/- 0.009 to 0.140 +/- 0.011, NS; m. brachioradialis 0.159 +/- 0.025 to 0.168 +/- 0.027, NS). This was accompanied by an increased extraction fraction of glucose, as measured by an increased arteriovenous difference over the forearm (0.16 +/- 0.04 to 0.70 +/- 0.10 mmol/l; P < 0.001) and by an increase in the estimated arterial-interstitial glucose difference in the gastrocnemius (0.82-1.42 mmol/l) and brachioradialis muscle (0.82-1.97 mmol/l). The blood flow in adipose tissue was significantly increased during insulin infusion, as evidenced by a decreased ethanol outflow-to-inflow ratio (0.369 +/- 0.048 to 0.325 +/- 0.046; P < 0.01). This was accompanied by an unchanged concentration of glucose in the dialysate (-2.6%, NS). In summary, during physiological hyperinsulinemia 1) a blood flow increase was detected in the calf and forearm, but not in the studied muscles of these limbs; 2) the blood flow increased in the subcutaneous adipose tissue; and 3) the estimated arterial-interstitial glucose difference increased in both muscles studied and was larger in the forearm muscle than the arteriovenous glucose difference over the forearm. The present study shows that microdialysis is a useful tool to obtain tissue-specific information about the effect of insulin on blood flow and glucose extraction in human skeletal muscle and adipose tissue.

Adipose Tissue↗

Effects of acetylcholine and nitroprusside on systemic and regional hemodynamics in hypertensive rats.

This study was performed to investigate the in vivo effects of acetylcholine, a stimulator of endogenous NO production, and nitroprusside, an exogenous NO-donor, on hemodynamics in the normotensive (WKY) and the hypertensive (SHR) rat. Anesthetized rats were given microspheres for the measurement of cardiac index (CI), total vascular resistance (TPRI), regional blood flow and vascular resistance. Infusion of acetylcholine (2 microg/kg/min) caused a marked decrease in TPRI by (-35+/-5%, +/-SEM) in the WKY (n=8), whereas in the SHR (n=8) a less pronounced reduction was seen (-14+/-3%, p<0.01 between groups). CI increased by 27+/-9% in the WKY, but was unaltered in the SHR. Blood pressure decreased similarly (17-20%). Acetylcholine significantly increased blood flow by about 40% in the kidneys and the heart in the WKY, but had no significant effect in the SHR. Other tissues, such as skeletal muscle and cerebral tissues, showed no major changes. Infusion of nitroprusside (1 microg/kg/min) reduced blood pressure by 5 to 10% in the strains. The regional effects of nitroprusside did not differ between the strains. In conclusion, the acetylcholine-induced vasodilation in the kidney and the heart was attenuated in the SHR compared to the WKY. These findings might suggest a difference in the endothelial response between the SHR and the WKY in some, but not in all, tissues.

Acetylcholine↗

Regression of left ventricular wall thickness during ACE-inhibitor treatment of essential hypertension is associated with an increase in insulin mediated skeletal muscle blood flow.

UNLABELLED: Left ventricular hypertrophy (LVH) has been associated with insulin resistance, a condition with an impaired insulin-mediated vasodilation in skeletal muscle. ACE-inhibitors have been reported to be superior to most other antihypertensive drugs in inducing a regression of LVH. In a double-blind study with parallel groups, 50 patients with essential hypertension were randomized to treatment with either fosinopril (20 mg o.d.) or atenolol (50 mg o.d.) for 12-16 weeks. Left ventricle wall thickness (LVWT, defined as the sum of interventricular septum and posterior wall), diastolic function (represented by the ratio between the E-wave and the A-wave of mitral blood flow) and femoral artery blood flow (FBF) were evaluated using ultrasonic measurements. FBF was measured at normoinsulinemia and after 2 h of euglycemic hyperinsulinemia. Before treatment, the insulin-induced increase in FBF was inversely related to the LVWT (r = -0.52, p < 0.02). The reduction in ambulatory 24-h SBP/DBP was 13/9 mmHg for fosinopril and 15/14 for atenolol, ambulatory DBP being significantly more reduced by atenolol (p = 0.03 for difference in treatment effect). However, only fosinopril treatment resulted in a significant reduction in LVWT (from 20.5 mm to 19.4 mm, p < 0.05). The degree of reduction in LVWT was related to the increase in FBF in the fosinopril group (r = -0.45, p < 0.05). For fosinopril (but not for atenolol), there was a positive relationship between the change in E/A ratio and the change in femoral artery stroke volume (r = 0.80, p < 0.01). CONCLUSION: Impaired insulin-induced stimulation of leg blood flow was related to an increased LVWT. Furthermore, during fosinopril treatment, regression of LVWT was associated with enhanced skeletal muscle blood flow during hyperinsulinemia. This indicates that impaired peripheral blood flow (and thereby increased afterload) may be a possible mechanism explaining the previously found association between insulin resistance and cardiovascular hypertrophy.

Adolescent↗

Regional haemodynamic differences between normotensive and spontaneously hypertensive rats--a microsphere study.

The objective of the present study was to compare systemic and regional haemodynamics in a large series of spontaneously hypertensive rats (SHR, n=32) with normotensive Wistar-Kyoto rats (WKY, n=26) at the age of 12-16 weeks. All rats were anaesthetized with thiobutabarbital and the radioactively labelled microsphere method was used to evaluate regional blood flow with special emphasis on different cerebral areas. The high blood pressure in the SHR was mainly due to elevated total peripheral resistance, which was 90% higher in the SHR compared to the WKY. Furthermore, heart rate was 25% (p<0.001) higher, but the cardiac index was lower by 20% (p<0.01) in the SHR. Blood flow was significantly lower and vascular resistance higher in several organs such as the kidneys, other visceral organs, skeletal muscle and skin of the SHR compared to the WKY. On the contrary, blood flow in the myocardium was augmented by 40% (p<0.01) in the SHR. Blood flow was 20-50% higher in the cerebral cortex, thalamus and caudatus (p<0.05-0.001), but attenuated in the hypophysis of the SHR. In the pons, medulla and cerebellum, blood flow was similar in the two strains. In this large microsphere study, the basal cardiac index was lower in the SHR already at this relatively early stage of established hypertension. Despite this, increased blood flow in the above mentioned cerebral regions was found in the SHR compared to the WKY.

Animals↗

Influences of carvedilol treatment on the effects of acetylcholine on regional haemodynamics in the spontaneously hypertensive rat.

1. In a previous report, we have shown that vasodilatation induced by acetylcholine is impaired in the kidney and the heart of the spontaneously hypertensive rat (SHR) in vivo. The present investigation was performed to study the influence of oral antihypertensive treatment with carvedilol for 6 to 10 weeks on acetylcholine-induced changes in regional haemodynamics in SHR in vivo. Cardiac output, regional blood flow and vascular resistance in organs of major importance in hypertensive disease, such as the kidney, heart, skeletal muscle, brain and eye, were measured with radioactively labelled microspheres in anaesthetized rats (aged 12-16 weeks).2. Mean arterial blood pressure was significantly lower in the carvedilol-treated SHR group (156+/-3 mmHg, n=17) than in an untreated SHR group (172+/-6 mmHg, n=13). Infusion of acetylcholine (2 microgram.min-1.kg-1) caused similar significant reductions in blood pressure in the two groups (-13+/-1% and -14+/-2%). However, acetylcholine induced a significant increase in total peripheral vascular resistance in the carvedilol group (29+/-10%, P<0.01), whereas no significant change was observed in the control group (0+/-11%).3. Acetylcholine significantly increased renal vascular resistance in the carvedilol group (+62+/-15%, P<0.01), but did not change vascular resistance in the control group (-6+/-6%). In the heart, acetylcholine did not affect vascular resistance in the carvedilol group, but reduced vascular resistance significantly in the control group (-17+/-8%, P<0.05). The circulatory changes induced by acetylcholine in the skeletal muscle, brain and ophthalmic circulation did not differ between the groups.4. In conclusion, the results demonstrate that long-term oral carvedilol treatment in the SHR did not enhance acetylcholine-induced vasodilatation, but instead pronounced renal vasoconstriction was induced by acetylcholine, which could partly be due to a decreased cardiac index.

Acetylcholine↗

Efficacy of a monocomponent pertussis toxoid vaccine after household exposure to pertussis.

In a double-blind, placebo-controlled efficacy trial of a monocomponent pertussis toxoid vaccine, 3450 infants were randomly assigned to vaccination with diphtheria-tetanus toxoids with or without pertussis toxoid at 3, 5, and 12 months of age. Study children and family members were investigated for possible pertussis with cultures, serology, and polymerase chain reaction. Efficacy was 71% after 3 dose when the World Health Organization case definition of pertussis (which includes paroxysmal cough for 21 days or longer) was used. We report the efficacy in the subgroup of children who were exposed to pertussis in the household. Among study children exposed to pertussis in the household from the day of the third vaccination, 20 of 99 (20%) recipients of diphtheria-tetanus-pertussis toxoids vaccine and 64 of 79 (81%) recipients of diphtheria-tetanus toxoids vaccine had pertussis fulfilling criteria of the World Health Organization. The vaccine efficacy was 75% (95% confidence intervals 64% to 84%). In children who had received only two doses at the time of household exposure, vaccine efficacy was 66% (95% confidence intervals 15% to 90%) based on 4 cases among 32 household-exposed recipients of diphtheria-tetanus-pertussis toxoids vaccine and 13 cases among 35 household-exposed recipients of diphtheria-tetanus toxoids vaccine. In conclusion, the pertussis toxoid vaccine provides protection against pertussis both after household and community exposure.

Diphtheria Toxoid↗

Serum calcium: a new, independent, prospective risk factor for myocardial infarction in middle-aged men followed for 18 years.

BACKGROUND: Primary hyperparathyroidism (HPT) is a disease characterized by hypercalcemia, and associated with an increased mortality in cardiovascular diseases. However, serum calcium levels within the normal range have not been evaluated as a prospective cardiovascular risk factor. METHODS: A cohort of males aged 50 (n = 2183) were investigated in 1970-1973 for serum calcium and known cardiovascular risk factors. They were then followed up over the next 18 years. RESULTS: During the follow-up period, 180 subjects experienced a myocardial infarction (MI). The serum calcium levels were significantly elevated at the baseline (2.37 +/- 0.09 SD versus 2.35 +/- 0.09 mmol/l, p < 0.03) in the subjects who developed a MI when compared with the rest of the cohort. Also blood pressure, body mass index (BMI), fasting insulin, serum cholesterol, serum triglycerides, and the atherogenic index were significantly elevated in the MI group (p < 0.01), while HDL-cholesterol was lower at the baseline investigation (p < 0.01). Cox's proportional hazard analysis showed that only serum calcium (p < 0.01), BMI (p < 0.0003), diastolic blood pressure (p < 0.0009), and the atherogenic index (p < 0.002) were significantly independent risk factors for MI. The range of serum calcium levels from the mean value, -2 SDs to the mean value +2 SDs corresponds to a variation in estimated risk for MI ranging from 0.06 to 0.15. CONCLUSIONS: Serum calcium was found to be an independent, prospective risk factor for MI in middle-aged males suggesting a role for extracellular calcium levels in the atherosclerotic process.

Calcium↗

The alterations in insulin sensitivity during angiotensin converting enzyme inhibitor treatment are related to changes in the calcium/magnesium balance.

The present analysis was undertaken to investigate the relations between alterations in mineral factors, especially the balance between serum calcium and magnesium concentrations (S-Ca and S-Mg, respectively), and variables reflecting glucose and lipid metabolism during angiotensin converting enzyme (ACE) inhibitor treatment. A total of 96 patients with essential hypertension, participating in four double-blind studies with four different ACE inhibitors and similar protocols, were included. At the end of the initial placebo period and at the end of the period of active drug treatment, a hyperinsulinemic euglycemic clamp test was carried out, lipoprotein status was assessed, and the concentrations of serum electrolytes were measured. The serum ACE activity was determined in the group treated with fosinopril. Changes in insulin sensitivity index (M/I) were directly correlated to alterations in S-Mg (r = 0.24, P < .02), and inversely correlated to changes in S-Ca (r = -0.19, P = .07) and the ratio between serum calcium and magnesium concentrations (Ca/Mg) (r = -0.27, P < .008). The change in total serum triglycerides (S-Tg) was inversely correlated to the change in S-Mg (r = -0.35, P < .0005), and directly correlated to the change in Ca/Mg ratio (r = 0.36, P < .0004). The reduction in serum ACE activity correlated to a more pronounced increase in S-Mg r = -0.62, P < .002), and decrease in the Ca/Mg ratio (r = 0.73, P = .0002). We conclude that the changes in the studied metabolic variables and serum ACE activity during ACE inhibitor treatment are related to alterations in mineral status and the balance between calcium and magnesium concentrations in serum.

Adolescent↗

Angioid streaks are part of a familial syndrome of dyserythropoietic anaemia (CDA III).

Congenital dyserythropoietic anaemia type III (CDA III) is a rare disease inherited in an autosomal dominant way and characterized by mild to moderate haemolytic anaemia. Most patients are adapted to their disease and have no or few complaints. Bone marrow examination shows a characteristic picture with erythroid hyperplasia and multinucleate erythroblasts. 20% of patients in a Swedish family affected with the CDA III condition have monoclonal gammopathy or multiple myeloma. By linkage and recombination analysis in the same family, the gene linked to the CDA III condition (CDAN3) has been located to chromosome 15q22. In this paper we report the observation of visual disturbances with macular degeneration and angioid streaks in six patients with CDA III and discuss the apparent association between CDA III, angioid streaks and monoclonal gammopathy. We suggest that this triad forms a previously unreported syndrome.

Adult↗

Serum levels of parathyroid hormone are related to the mortality and severity of illness in patients in the emergency department.

Hypocalcaemia is a common finding in intensive care patients. In addition, raised levels of parathyroid hormone (PTH) have been described. The explanation and clinical importance of these findings are yet to be revealed. To investigate the occurrence of hypocalcaemia and elevated PTH levels and their relationship to morality and the severity of disease, serum levels of PTH, ionized calcium (Ca2+) and the cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were measured on arrival in the emergency department in a broad spectrum of 140 acutely ill patients patients suffering from common diseases such as stroke, acute abdominal disorders, obstructive lung diseases, heart failure, acute myocardial infarction, angina pectoris, trauma and infectious diseases. A score (APACHE II) was calculated to assess the severity of disease. Elevated PTH levels (> 55 pg ml-1) were seen in 16% of the patients, being most frequent in patients with myocardial infarction (28%) and congestive heart failure (42%). The levels were significantly correlated with the APACHE II score (r = 0.48, P < 0.0001) and with the length of stay in hospital (r = 0.26, P < 0.002). PTH was also significantly (P < 0.03) elevated in non-survivors compared with survivors and was found to be a stronger predictor of mortality (P < 0.01) than the APACHE II score (P < 0.02) in Cox's proportional hazard analysis. No close relationships were found between the cytokine levels and the indices of calcium metabolism. In conclusion, a rise in serum levels of PTH was common and related to the severity of disease and mortality in a mixed emergency department population.

APACHE↗

Proinflammatory cytokines, measured in a mixed population on arrival in the emergency department, are related to mortality and severity of disease.

OBJECTIVES: To investigate whether serum levels of tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) are related to mortality and severity of disease in patients admitted to the Emergency Department (ED). DESIGN: Prospective cohort study. SETTING: Emergency Department of a tertiary university hospital. SUBJECTS: A total of 140 patients admitted to the ED, representing common acute medical diseases, such as stroke, obstructive lung disease, heart failure, myocardial infarction, angina pectoris, infectious diseases and acute abdominal disorders. MAIN OUTCOME MEASURES: APACHE II score at admission, hospital mortality and length of stay in hospital (LOS). RESULTS: A moderate rise in cytokine levels (IL-6; 50-300 ng L(-1), TNF-alpha; 10-70 ng L[-1]) was found in all diagnosis-groups, with the most pronounced elevation seen in patients with acute abdominal disorders (up to 6900 ng L[-1]). IL-6 on arrival to the ED was significantly correlated to the APACHE II score (r = 0.48, P < 0.0001), LOS (r = 0.36, P < 0.0001) and was elevated in nonsurvivors (n = 9) compared to those who did survive. TNF-alpha on arrival showed a significant correlation to LOS (r = 0.36, P < 0.0001) and APACHE II (r = 0.41, P < 0.0001), but was not associated to later mortality. CONCLUSIONS: Serum levels of proinflammatory cytokines collected at admission to the ED were related to the severity of disease and hospital mortality.

APACHE↗

Cardiovascular risk factors and electrographical characteristics and abnormalities in middle-aged males.

OBJECTIVES: To evaluate if characteristics and abnormalities found at the electrocardiogram (ECG) are related to common cardiovascular risk factors included in the insulin-resistance metabolic syndrome. DESIGN: Cross-sectional. SETTING: Tertiary university hospital. SUBJECTS: Over 2000 middle-aged males in whom ECG abnormalities were recorded, together with ECG characteristics measured in a random sample of men with no ECG abnormalities (n = 113). INTERVENTIONS: None. RESULTS: All three components of the metabolic syndrome; elevated blood pressure, dyslipidaemia and hyperinsulinaemia were found to be related to the heart rate (P < 0.002) and the QRS-duration (P < 0.01) and inversely to the QoT-interval (P < 0.05), the early diastolic phase (P < 0.05) and the T-wave amplitude (P < 0.02). The components of the metabolic syndrome was furthermore found to be associated with the occurrence of T-wave abnormalities (n = 64, P < 0.01) and to a lesser degree also to the occurrence of Q-waves (n = 21). CONCLUSIONS: The components of the insulin-resistance metabolic syndrome were related both to certain ECG characteristics in subjects with a normal ECG and to some ECG abnormalities. A raised sympathetic activity is likely to be the link between some of the described associations, whilst coronary heart diseases may explain others.

Blood Pressure↗

Circulating angiotensin converting enzyme levels are increased in concentric, but not eccentric, left ventricular hypertrophy in elderly men.

OBJECTIVE: To study the cross-sectional relationship between circulating angiotensin converting enzyme (ACE) activity and echocardiographically determined left ventricular geometry in a study of 380 70-year-old men participating in a health-survey reexamination and 50 patients with hypertension. METHODS: Two-dimensional guided M-mode and Doppler echocardiography. Fluorometric assay of serum ACE activity. RESULTS: The serum ACE activity was higher in the elderly men with left ventricular concentric hypertrophy than it was in men with normal geometry and left ventricular eccentric hypertrophy (32, 27, and 26 U/l, respectively, P < 0.01 for both comparisons before and after adjustment for the 24 h mean arterial pressure, body mass index, and use of antihypertensive medication). The serum ACE activity correlated with the thickness of the left ventricular interventricular septum (r = 0.12, P = 0.0095), the left ventricular relative wall thickness (r = 0.13, P = 0.0053 ), and the total peripheral resistance (r = 0.16, P = 0.0034), but not with the left ventricular mass (r = -0.039, P = 0.45) of these elderly men. The serum ACE activity in the hypertensive patients also correlated with the left ventricular interventricular septum thickness (r = 0.34, P = 0.020) independently of the 24 h mean arterial blood pressure, age, sex, body mass index, and insulin sensitivity. CONCLUSION: Levels of serum ACE activity are associated with left ventricular geometry.

Adult↗

Unchanged efficacy of a pertussis toxoid vaccine throughout the two years after the third vaccination of infants.

BACKGROUND: In a previously reported double blind efficacy trial of a pertussis toxoid vaccine, 3450 infants were randomized to receive diphtheria-tetanus toxoids with or without pertussis toxoid at 3, 5 and 12 months of age. Efficacy against pertussis as defined by the World Health Organization was 71% from 30 days after the third vaccination with an average follow-up of 17.5 months. We now report efficacy for an additional 6 months of open follow-up. METHODS: Parents were contacted monthly by a nurse. If a participant or a family member coughed for > or = 7 days, a nasopharyngeal sample and paired sera were obtained. RESULTS: Efficacy during this open follow-up period was 77% (95% confidence intervals, 66 to 85%) based on 29 and 110 cases fulfilling the WHO definition of pertussis in vaccinated and control children, respectively. Efficacy against household exposure was 76% (95% confidence intervals, 51 to 91%). Pertussis in vaccinated children had a significantly shorter duration than pertussis in control children. Determination of pertussis toxin antibodies in paired sera with enzyme-linked immunosorbent assay had a lower diagnostic sensitivity in vaccinated (45%) than in control (92%) children, while determination of antibodies against filamentous hemagglutinin (not included in the vaccine) was highly sensitive for diagnosing pertussis in both groups (100 and 90%, respectively). CONCLUSIONS: A monocomponent pertussis toxoid vaccine induces significant protection against pertussis for at least 2 years after the third injection. To obtain an unbiased estimate of vaccine efficacy it is important to determine antibodies against an antigen that is not included in the vaccine.

Antibodies, Bacterial↗