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C D Agardh

Publications and source records attributed to C D Agardh.

At least 73 records · Page 4Linked to original sources
PubMed1993

Tubular secretion of Tamm-Horsfall protein is decreased in type 1 (insulin-dependent) diabetic patients with diabetic nephropathy.

Signs of glomerular, proximal and distal tubular dysfunction as well as metabolic control were studied in type 1 diabetes mellitus. To that end, the urinary excretion rates of albumin, sodium, phosphate and Tamm-Horsfall protein as well as HbA1c levels were measured in 20 patients with different degrees of diabetic nephropathy (positive Albustix for several years). Eight diabetic patients with short duration of diabetes and without any diabetic complications and 10 apparently healthy subjects were studied for comparison. The HbA1c levels in the three groups were 8.6 +/- 1.2, 5.9 +/- 2.2 and 4.1 +/- 0.4%, respectively (mean +/- SD). Duration of diabetes in the two diabetic groups were 27 +/- 7 and 3 +/- 1 years, respectively. The urinary protein levels were measured by enzyme-linked immunoassays. The fractional clearance of sodium (1.9 +/- 1.9%; p < 0.001) and phosphate (27 +/- 11%; p < 0.01) were increased in patients with diabetic nephropathy compared to diabetic patients without nephropathy (0.6 +/- 0.2 and 16 +/- 4%) and healthy control subjects (0.6 +/- 0.1 and 16 +/- 4%, respectively). Tamm-Horsfall protein excretion rate was decreased in both diabetic groups (15.0x/3.1 and 37.9x/1.9 micrograms/min, geometric mean x/tolerance factor, p < 0.001 and p < 0.05, respectively) compared to the healthy subjects (63.8x/1.3 micrograms/min). Furthermore, patients with diabetic nephropathy had a lower excretion rate of Tamm-Horsfall protein (15.0x/3.1 micrograms/min) compared to patients without signs of nephropathy (37.9x/1.9 micrograms/min, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Distal blood pressure as a predictor for the level of amputation in diabetic patients with foot ulcer.

The predictive value of distal blood pressure measurements for the level of amputation was studied prospectively in 161 consecutive diabetic patients with foot ulcers. The patients were treated as outpatients except for periods of surgery and when complications requiring hospital care occurred. All patients were treated pre- and postoperatively by the same multidisciplinary foot care team. Either ankle or toe blood pressure measurement was available in 86% of the patients. Incompressible arteries, ulcer or gangrene at the measuring site, previous amputation, poor general condition, and an emergency situation were factors that excluded standardized ankle and toe blood pressure measurements in 24% and 27% of the patients, respectively. An absolute lower ankle pressure level of 50 mm Hg was found, below which a minor amputation was never sufficient to achieve healing. An ankle pressure below 75 mm Hg was seldom sufficient, and at or above that pressure level, the ankle pressure had no predictive value in this respect. At a toe pressure below 15 mm Hg, a minor amputation was seldom sufficient. Ankle and toe pressure indices gave no further information.

Adult↗
PubMed1992

Tubular secretion of Tamm-Horsfall protein in type 1 (insulin-dependent) diabetes mellitus using a simplified enzyme linked immunoassay.

The relationship between glomerular and tubular dysfunction and metabolic control in type 1 diabetes was studied. To that end the urinary excretion rates of albumin and Tamm-Horsfall protein as well as HbA1c levels were measured in 58 patients with different degrees of diabetic nephropathy and in 76 apparently healthy subjects matched for sex and age. The urinary Tamm-Horsfall protein levels were measured by a simplified enzyme linked immunoassay. The intra- and interassay variations were 8.9% and 13.6%, respectively. The intraindividual variation was 41% and the sensitivity of the assay was 4 micrograms/l. The Tamm-Horsfall protein excretion rate was 42.1 x/2.0 micrograms/min (geometric mean x/tolerance factor) in the diabetic patients compared to 34 x/1.9 micrograms/min in the control subjects (NS). The diabetic patients had higher albumin excretion rate (38.5 x/7.3 micrograms/min) than the control subjects (4.7 x/2.3 micrograms/min; P less than 0.001). By using multivariate analysis of variance, HbA1c level was found to be the only independent variable associated with Tamm-Horsfall protein excretion rate in diabetic patients (r = -0.28; P = 0.04), while no relationship was found between Tamm-Horsfall protein excretion rate and age, age at onset and duration of diabetes, gender, serum creatinine, diuresis, urinary albumin excretion rate, systolic and diastolic blood pressure levels and antihypertensive treatment. The urinary albumin excretion rate was associated with diastolic blood pressure (r = 0.34; P = 0.02) but not with HbA1c levels when testing the above variables by multivariate analysis of variance. In conclusion, these results may indicate a lack of relationship between glomerular and tubular dysfunction. The former was influenced only by diastolic blood pressure levels and the latter only by the degree of metabolic control. However, the correlations were weak and do not provide any insight into what is actually responsible for glomerular and tubular dysfunction.

Adult↗
PubMed1992

The influence of hypothermia on hypoglycemia-induced brain damage in the rat.

The effects of hypothermia on hypoglycemic brain damage were studied in rats after a 30-min period of hypoglycemic coma, defined as cessation of spontaneous EEG activity. The rats were either normothermic (37 degrees C) or moderately hypothermic (33 degrees C). Morphological brain damage was evaluated after various periods of recovery. Hypothermic animals with halothane anesthesia never resumed spontaneous respiration, thus requiring artificial ventilation during recovery (maximally 8 h). In contrast, when isoflurane was used as the anesthetic agent, all animals survived and were examined after 1 week of recovery. There was a tendency towards gradually higher arterial plasma glucose levels during hypoglycemia with lower body temperature. The time period from insulin injection until isoelectric EEG appeared was gradually prolonged by hypothermia, and was shorter when isoflurane was used for anesthesia. Brain damage was examined within the neocortex, caudoputamen and hippocampus (CA1, subiculum and the tip of the dentate gyrus). Damage to neurons was found to be of two types, namely condensed dark purple neurons (pre-acidophilic) and shrunken bright red-staining neurons (acidophilic). In the neocortex, no clear influence of temperature on the degree of injury was seen. In the caudoputamen, the number of injured neurons clearly decreased at lower temperature (33 degrees C, P less than 0.001) when halothane was used, while no such difference was seen when isoflurane was used as the anesthetic agent. Likewise, a protective effect of hypothermia was seen in subiculum (P less than 0.01) when halothane, but not isoflurane was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Regional cerebral blood flow in normal man during insulin-induced hypoglycemia and in the recovery period following glucose infusion.

The effect of moderate hypoglycemia (p-glucose, 2.0 +/- 0.3 mmol/L; mean +/- SD) on regional cerebral blood flow (rCBF) was studied in a group of 10 healthy, right-handed men (aged 23 to 28 years) using an intravenous xenon 133 single photon emission computed tomography technique (SPECT). After 10 minutes of hypoglycemia, global CBF had increased to 46.3 +/- 9.6 mL/100 g/min compared with the initial normoglycemic flow of 38.6 +/- 6.8 mL/100 g/min (P less than .01). The relative distribution of the rCBF changed significantly (P less than .05, ANOVA) from before to during hypoglycemia. Of the 10 regions analyzed, the highest increments in rCBF during hypoglycemia were found in the frontal (21.5% +/- 15.2%) and parietal (20.6% +/- 14.2%) lobes, and the lowest (10.7% +/- 9.4%) were found in the pons/brainstem regions. The increase in rCBF persisted for 15 minutes after normalization of blood glucose. The persisting high flow after hypoglycemia affected all regions, but a further 10.1% +/- 7.2% increase was observed in the pons/brainstem area (P less than .05). The CBF was significantly higher in the right compared with the left hemisphere (2.8%, 1.2%, and 3.9%, respectively; P less than .05) in all measurements. A decrease in brain volume was found at the final examination, compared with the hypoglycemic state (2.6%; P less than .05). It is concluded that moderate hypoglycemia leads to a marked increase in CBF and in the relative distribution of rCBF, which persists in the immediate period after normalization of the blood glucose level.

Adult↗
PubMed1992

The association between clinical risk factors and outcome of diabetic foot ulcers.

OBJECTIVE: The aim of the study was to describe the association between clinical risk factors in diabetic patients with food ulcers in relation to outcome. DESIGN: A prospective study of 314 consecutively presenting diabetic patients with foot ulcers referred to the Department of Internal Medicine between July 1, 1983 and June 30, 1987. All patients were followed to final outcome. SETTING: All patients were treated by the same multi-disciplinary foot care team at the Department of Medicine, both as in- and out-patients. Healing was defined as intact skin for at least 6 months. RESULTS: One hundred and ninety-seven patients healed primarily, 77 after amputation, and 40 died unhealed. Signs of macroangiopathy were more common among patients who healed after amputation. The outcome was strongly related to age, though 43% of the patients with an age over 80 years healed primarily. There was no difference in smoking habits between patients who healed primarily and those who required amputation to heal. Diabetic nephropathy was found in 26% of the patients and was strongly associated with amputation. Presence of retinopathy was found in 54% of the patients, but this finding was not related to the outcome. There were no differences in short-term metabolic control as assessed by hemoglobin A1c levels between patients who healed primarily and those who healed after amputation. CONCLUSION: The presence of diabetic foot ulcers was strongly associated with age and diabetic complications such as multiple cardiovascular disease and nephropathy, which were important factors related to amputation.

Adult↗
PubMed1992

Neuropsychological performance differs between type 1 diabetic and normal men during insulin-induced hypoglycaemia.

Cerebral function was measured with a neuropsychological test battery before, during, and after insulin-induced hypoglycaemia (blood glucose approximately 2.0 mmol l-1) in 10 male Type 1 diabetic patients (age 20-43 years, duration of diabetes 14 (2-30) years) and in 12 normal men. There were no group differences in neuropsychological results at normal glucose levels. Significant effects of hypoglycaemia were found in reaction-time measures (p less than 0.001) and in other tests requiring speed and attention (p less than 0.001), in verbal fluency (p less than 0.05), and short-term memory (p less than 0.001). Significant group effects and interactions (p less than 0.05) revealed that the diabetic patients were generally more affected by hypoglycaemia than the normal subjects. This might have been partly due to the larger absolute decrease in blood glucose level in the diabetic patients, although the rate of glucose decrease was not related to performance in either group. Thus, the diabetic brain might be more vulnerable to hypoglycaemia, perhaps through the persistent impact of repeated hypoglycaemic episodes, although no neuropsychological deficit is demonstrable at normal blood glucose levels.

Blood Glucose↗
PubMed1992

The response of regulatory peptides to moderate hypoglycaemia of short duration in type 1 (insulin-dependent) diabetes mellitus and in normal man.

The changes in plasma gastrin-releasing peptide (GRP), arginine vasopressin (AVP), neuropeptide Y (NPY), corticotropin releasing hormone (CRH), galanin, ACTH, cortisol, delta sleep-inducing peptide (DSIP), adrenaline, noradrenaline and pancreatic polypeptide (PP) were measured after 5 and 15 minutes of acute insulin-induced moderate hypoglycaemia (2.0 mmol/l) in 10 patients with Type 1 diabetes mellitus with no autonomic neuropathy and in 10 healthy subjects. Plasma catecholamine and PP levels rose in both groups in response to hypoglycemia and the secretory response of ACTH was lower in the diabetic subjects (p < 0.01). GRP concentrations increased during hypoglycaemia (p < 0.01) while a reduction in AVP occurred at the start of hypoglycaemia (p < 0.001). The plasma AVP concentrations were higher in the diabetic group compared with those in the normal group (p < 0.05). The NPY concentrations were higher in the normal subjects (p < 0.05) but no change in the mean level occurred in either group during hypoglycaemia. No group differences or changes in mean plasma concentrations were found for galanin, DSIP and CRH. These observations support the view that regulatory peptides, if involved in glucose homeostasis, may rather have a modulatory effect than a direct action in restoring normoglycaemia.

Adrenocorticotropic Hormone↗
PubMed1992

Growth hormone levels in the basal state and after thyrotropin-releasing hormone stimulation in young type 1 (insulin-dependent) diabetic patients with severe retinopathy.

Sixteen young patients with type 1 diabetes mellitus and rapidly progressive severe retinopathy were examined regarding serum levels of growth hormone before and after the i.v. administration of 200 micrograms thyrotropin-releasing hormone (TRH). Serum IGF I, HbA1c, blood pressure, urinary albumin, and serum creatinine levels were also measured. The control group consisted of type 1 diabetic patients matched for age, duration of diabetes and metabolic control with no or minimal background retinopathy. The results show that basal growth hormone levels were above normal in both groups, and that there was a paradoxical increment in growth hormone levels after TRH stimulation (p < 0.05) in patients with severe retinopathy, but the values did not differ from patients with background retinopathy. IGD I levels were normal in all patients but one, and no differences were seen between the two groups. HbA1c, serum creatine, blood pressure, and urinary albumin levels were similar in the groups but patients with severe retinopathy were treated with more insulin (p < 0.001). Thus, neither abnormal growth hormone levels, nor IGF I, seems to be associated with the development of severe retinopathy in young type 1 diabetic patients.

Adult↗
PubMed1992

[Diabetic nephropathy].

Diabetic nephropathy is a common complication in diabetes mellitus. In addition to the risk of renal failure, patients with established nephropathy are at increased risk of proliferative retinopathy and cardiovascular disease. As the earliest prodrome of nephropathy is microalbuminuria, albumin excretion needs to be monitored with a reliable method in all diabetics. In the event of microalbuminuria, diabetes treatment needs to be intensified to optimise metabolic regulation. Early institution of antihypertensive treatment is essential to avoid progression to clinical nephropathy.

Albuminuria↗
PubMed1991

The association between plasma beta-hexosaminidase and its isoenzyme patterns and retinopathy in type 1 diabetes mellitus.

beta-Hexosaminidase and its isoenzyme patterns were investigated in plasma from patients with Type 1 diabetes mellitus. The patients were divided into three main groups matched for duration of diabetes: (a) proliferative retinopathy (b), progress of retinopathy within a two-year period (c) and with no background retinopathy. When all patients were compared to a reference group, a significant increase of plasma beta-hexosaminidase activity was found. Patients with proliferative retinopathy had significantly increased activity of plasma beta-hexosaminidase compared to the reference group but not compared to the other diabetic patients. The isoenzyme distribution was not different in any of the diabetic subgroups compared to the reference group. It was also shown that various degrees of diabetic nephropathy did not influence total plasma Hex or the isoenzyme pattern.

Adult↗
PubMed1991

Free radical production and ischemic brain damage: influence of postischemic oxygen tension.

It is now becoming increasingly clear that free radicals contribute to brain damage in several conditions, such as hyperoxia and trauma. It has been more difficult to prove that free radical production mediates ischemic brain damage, but it has often been suggested that it may be a major contributor to reperfusion damage, observed following transient ischemia. Recent results demonstrate that cerebral ischemia of long duration, particularly when followed by reperfusion, leads to enhanced production of partially reduced oxygen species, notably hydrogen peroxide (H2O2). It has also been suggested that postischemic hyperoxia, e.g. an increased oxygen tension during the recirculation period, adversely affects recovery following transient ischemia. Other data support the notion that brain damage caused by permanent ischemia (stroke) is significantly influenced by production of free radicals. The present study, however, fails to show that recirculation following brief periods of ischemia (15 min) leads to an enhanced H2O2 production, and that hyperoxia aggravates the ischemic damage. This study was undertaken to reveal whether variations in oxygen supply in the postischemic period following forebrain ischemia in rats affect free radical production and the brain damage incurred. To that end, rats ventilated on N2O/O2 (70:30) were subjected to 15 min of transient ischemia. Normoxic animals were ventilated with the N2O/O2 mixture, hyperoxic animals with 100% O2, and hypoxic ones with about 10% O2 (balance either N2O/N2 or N2) during the recirculation. At the end of this period, the animals were decapitated for assessment of H2O2 production with the aminotriazole/catalase method. This method is based on the notion that aminotriazole interacts with H2O2 to inactivate catalase; thus, the rate of inactivation of catalase in aminotriazole treated animals reflects H2O2 production. In a parallel series, animals ventilated with one of the three gas mixtures in the early recirculation period, respectively, were allowed to recover for 7 days, with subsequent perfusion-fixation of brain tissues and light microscopical evaluation of the brain damage. Animals given aminotriazole, whether rendered ischemic or not, showed a reduced tissue catalase activity, reflecting H2O2 production in the brain. Hyperoxic animals failed to show increased tissue H2O2 production, while hypoxic ones showed a tendency towards decreased production. However, all three groups (hypo, normo- and hyperoxic) had similar density and distribution of neuronal damage. These results suggest that although postischemic oxygen tensions may determine the rates of H2O2 production, variations in oxygen tensions do not influence the final brain damage incurred.(ABSTRACT TRUNCATED AT 400 WORDS)

Amitrole↗
PubMed1991

Acidosis-induced ischemic brain damage: are free radicals involved?

Substantial evidence exists that reactive oxygen species participate in the pathogenesis of brain damage following both sustained and transient cerebral ischemia, adversely affecting the vascular endothelium and contributing to the formation of edema. One likely triggering event for free radical damage is delocalization of protein-bound iron. The binding capacity for some iron-binding proteins is highly pH sensitive and, consequently, the release of iron is enhanced by acidosis. In this study, we explored whether enhanced acidosis during ischemia triggers the production of reactive oxygen species. To that end, enhanced acidosis was produced by inducing ischemia in hyperglycemic rats, with normoglycemic ones serving as controls. Production of H2O2, estimated from the decrease in catalase activity after 3-amino-1,2,4-triazole (AT) administration, was measured in the cerebral cortex, caudoputamen, hippocampus, and substantia nigra (SN) after 15 min of ischemia followed by 5, 15, and 45 min of recovery, respectively (in substantia nigra after 45 min of recovery only). Free iron in cerebrospinal fluid (CSF) was measured after ischemia and 45 min of recovery. Levels of total glutathione (GSH + GSSH) in cortex and hippocampus, and levels of alpha-tocopherol in cortex, were also measured after 15 min of ischemia followed by 5, 15, and 45 min of recovery. The results confirm previous findings that brief ischemia in normoglycemic animals does not measurably increase H2O2 production in AT-injected animals. Ischemia under hyperglycemic conditions likewise failed to induce increased H2O2 production. No difference in free iron in CSF was observed between animals subjected to ischemia under hyper- and normoglycemic conditions. The moderate decrease in total glutathione or alpha-tocopherol levels did not differ between normo- and hyperglycemic animals in any brain region or at any recovery time. Thus, the results failed to give positive evidence for free radical damage following brief periods of ischemia complicated by excessive acidosis. However, it is possible that free radical production is localized to a small subcellular compartment within the tissue, thereby escaping detection. Also, the results do not exclude the possibility that free radicals are pathogenetically important after ischemia of longer duration.

Acidosis↗
PubMed1991

Urine and serum levels of the carboxyterminal domain (NCl) of collagen IV in membranous glomerulonephritis and diabetic nephropathy.

Serum and urinary concentrations of NCl, the non collagenous globular domain of collagen IV, were used as markers for turnover of basement membranes. NCl levels were studied in membranous glomerulonephritis and diabetic nephropathy. Thirteen patients with membranous glomerulonephritis and 8 insulin-dependent diabetic patients with diabetic nephropathy were compared to 16 apparently healthy control subjects. The patients with membranous glomerulonephritis had lower levels of NCl in serum and urine compared to the control subjects. In comparison, the patients with diabetic nephropathy had similar levels of NCl in serum and urine as the control subjects. Furthermore, among patients with membranous glomerulonephritis, those with hypertension had higher serum levels of NCl than those without, which may indicate that hemodynamic factors influence the basement membrane collagen metabolism. It is suggested that there are differences in basement membrane turnover in membranous glomerulonephritis and diabetic nephropathy although there are similarities in glomerular histopathological features. Other possible mechanism are discussed. Further studies are needed to confirm the suggested mechanism.

Adult↗
PubMed1991

Increased levels of plasma homocysteine are associated with nephropathy, but not severe retinopathy in type 1 diabetes mellitus.

The reactive vascular-injuring amino acid homocysteine was measured in plasma samples from 79 well-characterized type 1 diabetic patients and 46 control subjects. Patients with proliferative retinopathy had higher homocysteine levels (15.0 +/- 6.3 mumols l-1; mean +/- SD, p less than 0.001; n = 42) than those with progressive retinopathy during a two-year period (10.4 +/- 1.6 mumols l-1; n = 12), no or minimal retinopathy (10.7 +/- 4.3 mumols l-1; n = 25), and the control subjects (11.0 +/- 3.4 mumols l-1). Within the group of patients with proliferative retinopathy increased homocysteine levels were confined to those patients that had serum creatinine levels greater than 115 mumols l-1 and/or an albumin:creatinine clearance ratio greater than or equal to 0.02 x 10(-3) (17.0 +/- 5.9 mumols l-1; n = 23), whereas those with no or only minimal nephropathy had levels (12.1 +/- 5.5 mumols l-1; n = 18) that were not different from the control group. We conclude that neither type 1 diabetes mellitus nor diabetic retinopathy per se is associated with increased plasma homocysteine levels. In contrast, homocysteine accumulates, probably owing to reduced glomerular filtration, in diabetic patients with advanced nephropathy. This suggests that homocysteine might contribute to the accelerated development of macroangiopathy seen especially in this subgroup of diabetic patients.

Adult↗
PubMed1991

A study of exercise-induced microalbuminuria in type I (insulin-dependent) diabetes mellitus.

Microalbuminuria is thought to be an important prognostic factor in diabetes mellitus. To study the influence of changes in blood pressure on the development of microalbuminuria during exercise, two exercise tests were carried out. A total of 32 insulin dependent diabetic men whose age at onset was less than 30 years, mean duration of diabetes 14 years (range 7 to 21) and mean age 29 years (range 21 to 40), and who did not have albuminuria (N-labstix negative) were studied. The diabetic patients were compared with a total of 29 age-matched male control subjects. Urinary albumin excretion was measured during two exercise tests: at a standardised workload (150 W) for 30 min, and at a standardised heart rate for 25 min. The diabetic patients had higher albumin excretion rates during both exercise tests compared with the control subjects. Blood pressure and heart rate during exercise were significantly higher in diabetic patients compared with control subjects in the standardised workload test. If the test was individualised to achieve the same standardised heart rate there was no significant difference in blood pressure between the diabetic patients and the control subjects. These results indicate that the diabetic kidneys were more sensitive than the healthy kidneys to similar degrees of haemodynamic stress induced by exercise.

Adult↗
PubMed1991

Hydrogen peroxide production in ischaemic retina: influence of hyperglycaemia and postischaemic oxygen tension.

Free radicals have recently been proposed to play a role in the development of diabetic retinopathy. Ischaemia and hyperglycaemia followed by recirculation have been suggested to initiate free radical production in other tissues and the aim of the present study was to examine whether this could also be the case in the retina. The present study showed retinal cell damage, as measured by pycnotic cells, to be more pronounced when ischaemia was combined with hyperglycaemia than when combined with normoglycaemia. As an indication of free radical production, catalase activity was measured, reflecting the production of hydrogen peroxide (H2O2). Small amounts of H2O2 were found to be generated in the normal retina, but did not increase during ischaemia and hyperglycaemia followed by recirculation. It thus seems, as if hyperglycaemia aggravates the harmful effects of ischaemia, but with the methods used, there does not seem to be any increase in free radical production (as measured by H2O2 production) in normal rat retina during ischaemic and hyperglycaemic conditions.

Animals↗