Blunted epinephrine response following exercise in autonomic neuropathy.
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Biomedical subjects
Publications and source records attributed to B Lilja.
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To clarify the impact of autonomic neuropathy in diabetic patients, we have conducted a prospective study of 58 Type 1 and 51 Type 2 diabetic patients (investigated at baseline, after 4, and after 7 years). In Type 1 diabetic patients, the sympathetic nerve function (orthostatic acceleration and brake indices) and in Type 2 patients, parasympathetic nerve function (R-R interval variation; E/l ratio) deteriorated during 7 years of prospective observation. Symptoms of autonomic neuropathy were associated with signs of autonomic neuropathy (low brake indices) in Type 1 but not in Type 2 diabetic patients. In the latest assessment 24 h ECG recording was performed and blood samples assayed for neuropeptide Y (NPY) and motilin were obtained. Type 1 diabetic patients with parasympathetic neuropathy (abnormal E/l ratio) showed significantly lower SD value (less variation in the R-R intervals; 29 [17] vs 50 [16], [mean (interquartile range)]; p = 0.001) and higher postprandial plasma motilin values (70 [20] pmol l-1 vs 50 [15] pmol l-1; p < 0.01) than patients with normal parasympathetic nerve function. In Type 2 diabetic patients, sympathetic neuropathy (low brake indices) was associated with an increased frequency of ventricular extra systolic beats during 24 h ECG recording (rs = 0.65; p < 0.01). Postprandial plasma NPY levels were not associated with disturbed autonomic nerve function.
Iohexol and 99mTc-DTPA were used in 43 patients to determine the relative glomerular filtration rate (GFR), i.e., the GFR of each kidney in percent of total GFR. The amount of any GFR marker accumulating in Bowman's space, tubuli and renal pelvis within a few minutes after i.v. injection, before any marker had left the kidney via the ureter, was defined as proportional to the GFR of that kidney. The renal accumulation of iohexol was determined by CT using 10 slices of 8-mm thickness 1 to 4 minutes after injection. The renal accumulation of 99mTc-DTPA was determined with a gamma camera within 2 minutes after injection. The correlation coefficient between the two methods was 0.98. Due to the higher radiation dose from CT than from 99mTc-DTPA injection, relative GFR determination with CT should be performed when there is also a diagnostic need to reveal morphology.
OBJECTIVE: To study the effects of alternating cold and hot water therapy on walking ability and systolic blood pressure in claudicants. EXPERIMENTAL DESIGN: A prospective case study with repeated measurements before and 1, 4 and 12 months after treatment. The systolic blood pressure levels were measured with an occlusion cuff for brachial and ankle and with a strain gauge for the first toe. STUDY POPULATION: Twenty consecutively included patients, 11 women and 9 men; mean age 73.9 yrs, with intermittent claudication according to clinical examination and ankle-arm systolic blood pressure (AAI) below 0.90. INTERVENTION: Alternate hot and cold hydrotherapy of the legs were given at ten 25-minute treatments during a three-week period. The outcome measures were maximal walking ability (MW), walking ability before pain (PW) and systolic blood pressures of toe, ankle, arm and AAI. RESULTS: Fourteen patients (70%) reported reduced pain after treatment and their PW increased from 134 +/- 29 m to 415 +/- 119 m 12 months later (p < 0.05) and the MW in the total group increased form 348 +/- 75 m to 523 +/- 103 m. Systolic blood pressure increased in right ankle and toe one month after treatment in the total group. Among those who reported improved walking ability one year after treatment, systolic blood pressure in both right and left ankles and toes increased; e.g. right toe increasing from 72 +/- 7 to 86 +/- 2 (p < 0.001). Improvements of systolic blood pressure in left and right leg and changes of walking ability were correlated, in the order of 0.60 to 0.81, p < 0.05. CONCLUSIONS: Showering the legs of claudicants improved walking ability and blood pressures which sustained up to 1-year later. This therapy might be an additional alternative to conservative treatment of intermittent claudication.
To evaluate the effect of acute blood pressure (BP) changes on the myocardial perfusion in hypertensives, 10 patients with and 10 patients without left ventricular hypertrophy (LVH) were examined with 99TCm-Sestamibi scintigraphy at rest and after acute pharmacological BP reduction using nifedipine and captopril. Signs of LV ischaemia was quantified as the size of the hypoperfused area defined as isotope uptake below 70% of maximum LV uptake, and LVH was defined as ventricular mass (LVM) > 125 g/m2 BSA by use of echocardiography. Not significant relations between BP and size of the hypoperfused area was found at rest. During BP reduction patients with LVH had negative correlations (r = -0.58) between the size of the hypoperfused area and the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) (r = -0.49) while patients without LVH showed positive correlations (SBP r = 0.60, DBP r = 0.48). The differences in correlation coefficients were significant (P < 0.01) for both. Thus, in hypertensives with LVH, ischaemia may develop at low BP providing a possible mechanism for the observed increased risk of cardiovascular events in some hypertensive patients with low achieved BP during follow-up. Until treatment goals are defined on scientific grounds, BP should not be decreased below 90 mm Hg in subjects with LVH.
To clarify whether GAD-ab are associated with diabetic autonomic neuropathy and/or complement fixing antibodies against sympathetic ganglia, adrenal medulla, and vagus nerve, we examined 133 diabetic patients (95 with IDDM). GAD-ab were determined by a radioligand binding assay using in vitro expression of recombinant GAD-65 whereas sympathetic ganglia antibodies, adrenal medulla antibodies, vagus nerve, and ICA were evaluated by indirect immunofluorescence assays. Autonomic nerve function was evaluated by objective tests (heart rate reactions to deep breathing and to tilt). In the total material of 133 patients, GAD-ab were detected in 36 patients, all of whom had IDDM. The frequency of GAD-ab was similar (38%) in IDDM patients with and without signs of autonomic neuropathy (21 of 55 vs 15 of 40). In addition, there were no significant associations between GAD-ab and autonomic nerve antibodies; GAD-ab were detected in 9 of 21 (43%) of patients with and in 27 of 112 (24%) of patients without sympathetic ganglia antibodies, in 5 of 15 (33%) of patients with and 31 of 118 (26%) without adrenal medulla antibodies, and in 5 of 15 (33%) with and 31 of 118 (26%) of patients without vagus nerve antibodies. The frequency of ICA, however, was significantly increased in patients with sympathetic ganglia antibodies compared with those without sympathetic ganglia antibodies (10 of 21 [48%] vs 21 of 112 [19%]; p < 0.01). In conclusion, GAD-ab were neither associated with disturbed autonomic nerve function nor with antibodies against autonomic nerve structures.
Cardiac pheochromocytoma is a rare tumour and may be difficult to localize. We present a 32-year-old male with a cardiac pheochromocytoma that was successfully resected. An initial unenhanced CT did not reveal the tumour. MIBG-scintigraphy indicated the location, but to get full information, a dynamic contrast-enhanced CT of the chest during adequate alpha and beta blockade was essential. ECG-gated MRI gave further information about the anatomical details.
To clarify whether long-term impaired glucose tolerance (IGT) is associated with dysfunction of peripheral and autonomic nerves, age-matched men with IGT and diabetes mellitus were followed prospectively for 12-15 years, when peripheral and autonomic nerve function was assessed. The patients comprised four subgroups: (1) 51 IGT subjects (duration of IGT at least 12-15 years); (2) 35 diabetic patients, with IGT 12-15 years ago, who later developed diabetes; (3) 34 diabetic patients, duration of diabetes at least 12-15 years; and (4) 62 age-matched non-diabetic control subjects. Mean age of the whole study population was 61 +/- 2 years (mean +/- SD), not different in the four groups. Peripheral nerve function tests included nerve conduction velocities, amplitudes, distal latencies, F-reflexes, and sensory perception thresholds for heat, cold, and vibration. Autonomic nerve function tests included the heart rate reaction during deep breathing (expiration to inspiration ratio) and to tilt (acceleration and brake indices). Despite 12-15 years of IGT, peripheral nerve function did not differ between IGT and control subjects, whereas autonomic nerve function deviated; an abnormal expiration to inspiration ratio (a sign of vagal nerve dysfunction) was significantly more common (15/51 versus 5/62; p < 0.01) in IGT than in control subjects. Diabetic patients (groups 2 and 3) showed lower conduction velocities (in general 2-4 m s-1 lower) than IGT and control subjects in all tested nerves. In conclusion, diabetes but not IGT, is associated with peripheral nerve dysfunction.
The major salivary glands were examined with 99m-Tc-pertechnetate scintigraphy in randomly selected subjects with (n = 30) and without (n = 12) symptoms of dry mouth and/or eyes, and in patients with primary Sjögren's syndrome (1 degree SS, n = 17). The scans were quantitatively evaluated and compared to other objective tests used to diagnose 1 degree SS. As compared with those for asymptomatic subjects, most values for the scintigraphic variables were non-significantly lower for symptomatic subjects and the time-activity curves were slightly flatter for all major salivary glands. In patients with 1 degree SS most values for the scintigraphic variables were significantly lowered and the submandibular glands were the glands most affected, as reflected in a flat time-activity curve, while the parotid glands were mainly affected during stimulated secretion. The scintigraphic variables correlated with the self-rated dryness of mouth in symptomatic subjects and with the abnormality of sialometry results in patients with 1 degree SS. We conclude that salivary gland scintigraphy is a sensitive and valid method to measure salivary gland function and abnormalities.
99Tcm-Sestamibi has now replaced 201Tl as a cardiac imaging agent. In addition to the myocardial uptake there is also a considerable uptake in the striated muscle, which may be used for analyzing the muscular perfusion. Sixteen patients with intermittent claudication were investigated with 99Tcm-Sestamibi-SPECT (single photon emission computerized tomography) in order to visualize coronary ischemic disease. After the registration of the myocardial perfusion they were also studied regarding their leg muscle perfusion. This was done at rest and during standardized stress test using a bicycle ergometer. In 10 of the patients there was an increase in the isotope uptake in the myocardium from work to rest > 10% reflecting pronounced myocardial ischemia, which, however, was symptomatic in only 4 of the patients. The muscular uptake in the myocardium of 99Tcm-Sestamibi in the thigh increased significantly from rest to exercise (P < 0.01), while it remained unchanged in the calf muscle. There were no significant correlations at rest between the ratio of the right and left systolic blood pressure in the ankles and the ratio between the right and left isotope uptake in the calves, but the increase in the isotope uptake from rest to work correlated with the blood pressure ratio at r = 0.79, P < 0.01 (anterior projection) and r = 0.71, P < 0.01 (posterior projection).
OBJECTIVE: To evaluate whether autonomic neuropathy predicts deterioration in glomerular filtration rate in IDDM patients. RESEARCH DESIGN AND METHODS: A prospective study in which 35 IDDM patients have been followed for 10-11 yr. Autonomic nerve function tests included heart-rate reactions to deep breathing (expiration-to-inspiration ratio) and to tilt (acceleration and brake indexes). GFR was evaluated by the 51Cr-EDTA plasma clearance method. RESULTS: At entry to the study, no significant differences were noted in age (39 +/- 2 [mean +/- SE] vs. 42 +/- 4 yr), duration of diabetes (20 +/- 3 vs. 23 +/- 4 yr), supine blood pressures (120/79 +/- 3/2 mmHg vs. 121/78 +/- 6/3 mmHg), and GFR (113 +/- 6 vs. 107 +/- 3 ml.min-1.1.73 m-2) between 20 patients with and 15 without autonomic neuropathy (age-corrected criteria). After 10-11 yr, GFR had decreased significantly (22 +/- 4 ml.min-1.1.73 m-2, P < 0.001) in patients with autonomic neuropathy but not (8 +/- 5 ml.min-1.1.73 m-2, NS) in patients without. In keeping with this, GFR decreased more than expected (difference in GFR/expected decrease in GFR) in patients with autonomic neuropathy, compared with those without (4.46 +/- 0.98 vs. 0.48 +/- 0.73, P < 0.005). CONCLUSIONS: Autonomic neuropathy predicts future deterioration in GFR in IDDM patients.
Autonomic nerve function was evaluated in 40 patients with total ulcerative colitis and in 25 patients with irritable bowel syndrome by three established non-invasive tests based on the heart reactions to deep breathing (E/I ratio) and tilt (acceleration and brake index). None of the patients were diabetic. Most of the patients with ulcerative colitis were clinically and biochemically inactive; 10 had previously undergone colectomy. The results were compared with a control group consisting of 56 healthy individuals and 33 previously investigated patients with Crohn's disease, 45% of whom demonstrated autonomic neuropathy (AN). Patients with ulcerative colitis had a significantly lower E/I ratio than controls in age-corrected values, indicating vagal nerve dysfunction. Altogether, 35% had signs of AN. In patients with irritable bowel syndrome 36% had evidence of AN, a figure in agreement with observations from other investigators. We conclude that AN is common in patients with ulcerative colitis, regardless of disease activity and previous colectomy. In contrast to a predominantly sympathetic dysfunction in Crohn's disease, AN in ulcerative colitis was vagal.
Quantitative bone scintigraphy was performed in 24 patients with prostatic carcinoma before orchiectomy and up to one to four years after operation. The gamma camera count rate was recorded over the lower thoracic and all lumbar vertebrae 4 h after injection of 99mTc-MDP. Twelve patients had normal bone scintigrams throughout the study. They showed from two years after operation a slight increase in count rate values compared with the preoperative values, probably due to hormonal changes after orchiectomy and to age-related alterations in skeletal metabolism. Twelve patients had abnormal bone scintigrams. They showed as a response to treatment the flare phenomenon with an increase in count rate over the abnormal vertebrae when measured two weeks after operation followed by a decrease after two months. The lowest count rate values were obtained between six months and one year after operation. Thereafter the count rate seemed to remain on the same level. An increase in count rate was connected to progression of disease and the patients died of prostatic carcinoma within one year thereafter.
To clarify a possible relationship between the level of BP and signs of myocardial ischaemia, two groups of treated hypertensive patients with (n = 12) and without (n = 18) increased left ventricular mass defined by echocardiography were investigated with 24h ambulatory BP and ECG monitoring. It was found that hypertensive patients with increased left ventricular mass had the following. (1) Higher systolic BP, heart rate (HR) and SBP x HR product during the night indicating a higher ventricular work load than hypertensives without increased LVM in this period. (2) This increased left ventricular work load during the night was concomitant with a lower DBP consistent with a lower perfusion pressure of the left ventricular myocardium. (3) Significantly depressed ST segment levels throughout the 24 hours with a significant positive correlation between BP and the level of the ST segment indicating increased ischaemic metabolic changes within the myocardium the lower the BP. (4) A higher ratio between the systolic SBP x HR product and DBP during sleep than in hypertensives without increased left ventricular mass, further corroborating that low DBP during the night might cause ischaemia through an imbalance between left ventricular work load and coronary perfusion pressure. We conclude that low BPs in hypertensive patients with increased left ventricular mass seem to induce ischaemia of the left ventricle. These findings provide a possible mechanism for the increased risk of ischaemic heart disease in hypertensive patients with low achieved BP.
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Plasma neuropeptide Y (NPY), plasma galanin and plasma catecholamines were determined before and during an ergometer exercise test in 11 type 1 diabetic patients (age 19-36 years, mean 30; duration of diabetes 2-18 years, mean 9) with autonomic dysfunction and in 13 age-matched healthy controls (age 24-36 years, mean 29). Before exercise, plasma NPY (100 +/- 6 pmol/l vs 144 +/- 7 pmol/l; P less than 0.001) and plasma galanin (54 +/- 3 pmol/l vs 77 +/- 5 pmol/l; P less than 0.005) were significantly lower in patients than in controls. During exercise, plasma NPY, plasma adrenaline, and plasma noradrenaline increased in patients and controls while galanin only increased in patients. Since there was a direct correlation between plasma NPY before exercise and the increment (delta 80%) in noradrenaline during exercise (r = 0.54; P less than 0.01), it is suggested that plasma NPY determined in the basal situation may be a useful marker of sympathetic nerve failure in diabetic patients.
The cardiovascular responses to tilting and breathing were studied in 24 patients with late-onset Alzheimer's disease (AD) and 54 healthy control women aged between 75 and 96 years in order to study the parasympathetic and sympathetic heart-rate control. The cardiovascular response to tilting and breathing showed no age-associated decrease in the healthy control women. During rest, the AD patients had lower mean systolic and diastolic blood pressure but the same heart rate as the control patients. After tilting, the AD patients had a greater increase in heart rate, and the mean systolic blood pressure fell to 126 mmHg compared with 160 mmHg in the control women (p less than 0.001). After the initial acceleration, the following deceleration of the heart rate, an expression of parasympathetic nervous activity, was lower in the AD patients (p less than 0.001). The deep-breathing test showed no significant difference between the two groups, but the changes of acceleration and brake indices could indicate a dysfunction of the autonomic nervous system since the AD patients were not recumbent.
This study presents the outcome of myocardial scintigraphy performed before and after thrombolytic treatment in 16 patients with acute myocardial infarction using 99Tcm-Sestamibi (Cardiolite, Du Pont Scandinavia AB, Kista, Sweden). The patients were given 99Tcm-Sestamibi intravenously as soon as possible after the decision to give thrombolytic treatment. When the patients were in a clinically stable state after the thrombolytic treatment, myocardial perfusion was analysed with the gamma camera using single photon emission computerized tomography (SPECT). A second 99Tcm-Sestamibi tomography was carried out on the second to fourth day after the myocardial infarction. Data reconstruction was done with the 'Bull's eye technique'. Nine patients received thrombolysis < 3 h from the onset of pain. In this group six patients (66%) improved their myocardial perfusion by > 10% after treatment, while all seven patients who received treatment > or = 3 h after the onset of pain improved their myocardial perfusion by < 10%. This study emphasises the importance of early diagnosis and treatment of patients with acute myocardial infarction in order to salvage myocardium.