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Biomedical subjects

A Kofoed-Enevoldsen

Publications and source records attributed to A Kofoed-Enevoldsen.

At least 19 recordsLinked to original sources
PubMed2004

Long-term postoperative mortality in diabetic patients undergoing major non-cardiac surgery.

BACKGROUND AND OBJECTIVE: The prognosis of diabetic patients after surgery remains controversial. Some suggest that the rates of death and complications today are almost identical in diabetic and non-diabetic patients within hospital stay or for 30 days postoperatively, whereas others suggest that diabetes still constitutes a major risk factor for both short-term (< or = 30 days) and long-term (> 30 days) patients especially after major cardiac surgery. We examined the long-term postoperative mortality of diabetic patients undergoing major non-cardiac surgery to identify possible perioperative risk factors. METHODS: Data from 179 consecutive diabetic patients, who underwent major non-cardiac surgery at Herlev Hospital, Denmark, during a 12 month period, have been retrospectively analysed. Data were obtained from patient records and from The Danish National Health Register. The main outcome measure was postoperative mortality. Patients were followed for a maximum of 18 months. RESULTS: The median postoperative observation period was 10 months (range 0-18 months). Overall postoperative mortality was 24% (95% confidence interval (CI) 17-31%). One third of the fatalities occurred during the first 30 days. Ischaemic heart disease diagnosed before the operation was associated with an overall postoperative mortality of 44% (95% CI 29-58%), which was significantly (P < 0.03) higher than in diabetic patients without known cardiovascular disease. The major causes of death in 18 out of 39 (46%) patients were diseases of the cardiovascular system. CONCLUSIONS: Diabetic patients undergoing major non-cardiac surgery seem to have a high mortality, often because of cardiovascular death. Future strategies should focus on implementing cardio-protective treatment during the perioperative period.

Adult↗
PubMed2002

Single determination of plasma ACTH using an immunoradiometric assay with high detectability differentiates between ACTH-dependent and -independent Cushing's syndrome.

The purpose of this retrospective study was to elucidate the value of an ACTH assay with high detectability to differentiate between ACTH-dependent and -independent Cushing's syndrome. The study was based on the case records of 56 patients with Cushing's syndrome comprising 34 patients with ACTH-dependent Cushing's syndrome and 22 patients with ACTH-independent Cushing's syndrome. Basal morning plasma 1-39 ACTH was measured using an immunoradiometric assay (IRMA) with a normal range of 1.8-11 pmol/L. Peripheral corticotrophin-releasing hormone (CRH) tests were performed in 24 and 17 patients with ACTH-dependent and -independent Cushing's syndrome, respectively. Using a single ACTH measurement, a complete separation was observed between the two defined groups, with a cut-off value of 2.4 pmol/L. Mean ACTH concentration was 14.4 pmol L (range 2.5-47.7 pmol/L) in ACTH-dependent Cushing's syndrome and 0.6 pmol/L (range 0.2-2.2 pmol/L) in ACTH-independent Cushing's syndrome. The range of separation between the two groups was further increased by using two ACTH measurements in each patient or peripheral stimulation with CRH. It is concluded that in the majority of patients with Cushing's syndrome a single basal morning ACTH determination is sufficient to discriminate between ACTH-dependent and ACTH-independent Cushing's syndrome. In borderline cases with ACTH in the range 2-3 pmol/L, repeated measurements might be necessary. The peripheral CRH test was not superior to repeated ACTH measurements.

Adrenocorticotropic Hormone↗
PubMed1999

Pulmonary damage after modest exposure to zinc chloride smoke.

Thirteen soldiers (11 men and two women) were exposed to zinc chloride smoke (ZCS) during a combat exercise. Even though their initial symptoms were modest, a prolonged follow up with lung function testing and blood samples was undertaken due to previous cases with fatal outcome after exposure to ZCS. Four weeks after exposure there were statistically significant declines from baseline values in lung diffusion capacity and total lung capacity of 16.2% and 4.3%, respectively. At the same time plasma levels of fibrinogen and zinc were significantly elevated, though mainly within the normal range. All variables showed a tendency towards normalization at follow up 8 weeks and 6 months after exposure. These findings indicate an unexpected quantifiable damage to lung parenchyma with a remarkable delay after modest exposure to zinc chloride smoke despite sparse initial symptoms. Exposure to high concentrations of ZCS may induce adult respiratory distress syndrome (ARDS) after a symptom free period of up to 12 days from exposure. Even though none of the soldiers in the present study developed ARDS the assessment of lung diffusion capacity and acute phase reactants is proposed as a supplement when monitoring patients after exposure to ZCS.

Adult↗
PubMed1999

Glucosaminyl N-deacetylase mRNA expression in diabetic rats.

Glucosaminyl N-deacetylase is a key enzyme in the synthesis of heparan sulphate. N-deacetylase activity is inhibited in experimental diabetes. The mechanism by which diabetes influences N-deacetylase activity is unknown. Using reverse transcription PCR we quantified hepatic N-deacetylase mRNA in normal and streptozotocin diabetic rats. A negative correlation was found between final blood glucose and N-deacetylase mRNA expression in diabetic rats, r = -0.44, p < 0.05. N-deacetylase mRNA expression was also correlated to N-deacetylase activity (r = 0.48, p < 0.05). N-deacetylase:cyclophilin mRNA ratio was not significantly affected by diabetes, 0.26 (0.2-0.35) vs 0.31 (0.16-0.5), p =0.48, in 10 weeks and 0.21 (0.15-0.37) vs 0.27 (0.19-0.32), p = 0.65, in 8 months rats, diabetic and normal rats respectively, median (interquartile range). The negative correlation between blood glucose and N-deacetylase mRNA in diabetic rats suggests however that altered gene expression may contribute to the altered N-deacetylase activity seen in experimental diabetes.

Amidohydrolases↗
PubMed1997

[Zinc chloride smoke pollution. Effects of minimal exposure].

Thirteen patients were exposed to accidental zinc chloride inhalation during an army exercise. Smoke bombs were released in open air. The exposure was modest ranging from "taking a few inhalations" to "5-10 minutes in a house with smoke drifting in through unshuttered windows". Initial symptoms were scanty. All patients received inhalation steroid on admittance followed by i.v. bolus of hydrocortisone. Four patients continued systemic steroid treatment (prednisolone 40 mg with stepwise reduction to zero over four weeks) because exposure was judged significant (> 1 minute of unprotected inhalation). No respiratory symptoms developed within an eight week observation period. However, a gradual decline in pulmonary CO diffusion capacity (to 85% (76-99 of initial capacity) was observed within the first four weeks. It is concluded that a very modest inhalation of zinc chloride smoke may induce prolonged impairment of pulmonary function.

Adult↗
PubMed1996

Effects of heparin and aminoguanidine on glomerular basement membrane thickening in diabetic rats.

The effects of heparin and aminoguanidine on glomerular basement membrane thickening were studied in streptozotocin diabetic Sprague-Dawley rats. A placebo-treated group and a non-diabetic group served as controls. All diabetic rats remained severely hyperglycaemic (23 mmol/l) throughout the 8-month study period. At the end of this time relative kidney weight was significantly increased in diabetic control rats (4.9 +/- 0.5 g/kg b.w.) compared with non-diabetic rats (3.3 +/- 0.3 g/kg). This increase was not affected by the intervention treatments. Glomerular basement membrane thickness increased 32% in diabetic control rats (240 +/- 24 nm) compared with non-diabetic rats (182 +/- 20 nm). This increase was prevented by s.c. treatment with both unfractionated and low molecular weight heparins, while basement membrane thickness was the same in animals treated with oral heparins and aminoguanidine and untreated diabetic rats. Macroscopic malignant kidney tumours were seen in three aminoguanidine-treated rats. In conclusion, subcutaneously administered heparin prevents diabetes-induced glomerular basement membrane thickening.

Administration, Oral↗
PubMed1996

Evidence of impaired glomerular charge selectivity in nondiabetic subjects with microalbuminuria: relevance to cardiovascular disease.

Microalbuminuria is associated with excess cardiovascular morbidity and mortality in diabetic and nondiabetic subjects. Loss of glomerular charge selectivity may explain the development of microalbuminuria in diabetic subjects. The primary population in this cross-sectional study was 124 subjects aged 40 to 75 years without glucose intolerance and with a previous (3 years before the present study) urinary albumin excretion rate (UAE) in the normal (<20 microgram/min) or microalbuminuric (>20 microgram/min) range. The secondary population consisted of 39 offspring aged 15 to 40 years. The main outcome measures included UAE, urinary IgG/IgG4 selectivity index (SI), and the presence of ischemic heart disease as determined by questionnaire or ECG. Among the primary population, a significant inverse correlation was found between SI and UAE (r=-.40, P<.001). Reduction in SI could be demonstrated in subjects with UAE >10 microgram/min. In multiple regression analysis reduction in SI was found with increasing age, independent of UAE. In 20 subjects with clinical cardiovascular disease a reduction in SI was found (1.9+/-0.6 versus 2.6+/-1.3, P=.001) without concomitant elevation in UAE (P=.99). Offspring from parents with microalbuminuria had an SI comparable to offspring from parents with normal UAE (2.7+/-0.7 versus 3.3+/-1.6, P=.17). In nondiabetic subjects the development of microalbuminuria is associated with reduced SI, suggesting impairment of glomerular charge selectivity. SI may offer a more sensitive monitoring of abnormalities in glomerular permselectivity than does measurements of UAE, but the ability of SI to predict development of cardiovascular disease needs to be evaluated prospectively.

Adolescent↗
PubMed1995

Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus.

We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU unfractionated heparin, or 2000 anti-Xa IU low-molecular-weight heparin. Unfractionated and low-molecular-weight heparin induced a significant reduction in urinary albumin excretion (p = 0.04 and p = 0.004). The mechanism and clinical relevance is unknown but deserve further attention.

Adult↗
PubMed1995

Na+/H+ exchanger isoform-1 abundance in skin fibroblasts of type I diabetic patients with nephropathy.

In diabetic nephropathy and essential hypertension, the cellular Na+/H+ exchanger (NHE) exhibits increased activity. Whether this reflects increased numbers of NHE isoform-1 (NHE-1) transporters or increased turnover per molecule has not been established. We have used a specific polyclonal antibody directed toward the C-terminal of NHE-1 to measure NHE-1 content in cultured skin fibroblasts from diabetic patients with (DN) and without (DCON) nephropathy and normal controls (CON). NHE-1 content in fibroblasts from DN subjects was significantly less than that in the other two groups. This suggests that increased NHE activity in diabetic nephropathy is attributed to increased NHE-1 turnover per site rather than increased NHE-1 expression.

Adult↗
PubMed1995

Diurnal variation in glomerular charge selectivity, urinary albumin excretion and blood pressure in insulin-dependent diabetic patients.

The urinary albumin excretion rate (AER) in a subgroup of patients with insulin-dependent diabetes mellitus (IDDM) steadily increases. In these patients a concomitant reduction of the glomerular charge selectivity index (SI) has been demonstrated. The aim of the present study was to evaluate whether diurnal variation in AER could be related to a diurnal variation in SI and/or a diurnal blood pressure variation. Thirty-three patients with IDDM, 27 with normal albumin excretion (AER < 20 micrograms/min; group D(o)) and six with incipient nephropathy (AER from 20 to 200 micrograms/min; group DA), were studied. AER and SI (renal clearance ratio of total-IgG/IgG4) were measured in three different urine collecting periods: period A (8:00 a.m. to 12:00 a.m.), period B (12:00 a.m. to bedtime) and period C (bedtime to 8:00 a.m.). A significant increase in SI was seen during the nighttime: period A, 1.6 (0.2 to 3.8; mean, range); period B, 1.7 (0.3 to 3.0); and period C, 2.0 (0.2 to 4.0); P = 0.01. Corresponding to this observation, an overall significant decrease in AER was found: period A, 10 (3 to 137) micrograms/min (median, range); period B, 8 (3 to 84) micrograms/min; and period C, 5 (0 to 78) micrograms/min; P < 0.001. In all three sampling periods a negative correlation was found between AER and SI. When group D(o) was analyzed alone, the results were similar. Diurnal variation in blood pressure was significantly positively correlated with AER in group DA, but was not correlated to variation in AER in D(o). We suggest that in normoalbuminuric IDDM patients diurnal variation in AER is related to diurnal variation in SI.

Adolescent↗
PubMed1994

Glomerular size- and charge selectivity in type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy.

In an attempt to evaluate the mechanisms of proteinuria in diabetic kidney disease, we measured the renal clearances of albumin, total IgG, and IgG4 in 20 male Type 2 (non-insulin-dependent) diabetic patients with diabetic glomerulosclerosis (biopsy proven), in 10 male Type 2 diabetic patients without nephropathy (urinary albumin excretion rate < or = 30 mg/24 h), and in 10 healthy male subjects. The fractional clearance of albumin was increased in patients with nephropathy: 659 (42-4355) x 10(-6) (median (range)), compared to 2.6 (0.2-14.2) x 10(-6) in patients without nephropathy, and 2.3 (0.4-4.2) x 10(-6) in healthy subjects. The fractional clearance of total IgG (neutral) and of IgG4 (anionic) was 40-50 times higher in patients with nephropathy compared to the two other groups. The IgG/IgG4 selectivity index was not significantly different in the three groups, being: 1.12 (0.06-5.65), 1.16 (0.45-3.72) and 1.35 (0.65-3.34) in patients with nephropathy, patients without nephropathy, and healthy subjects, respectively. The IgG/albumin selectivity index was decreased in patients with nephropathy: 0.27 (0.01-1.26) compared to 1.29 (0.07-2.67) (p < 0.05) and 1.23 (0.76-7.84) (p < 0.001) in patients without nephropathy and healthy subjects, respectively. No significant change in IgG/albumin selectivity index was observed between patients without nephropathy and healthy subjects. The systolic blood pressure was elevated in the patients with nephropathy: 164 +/- 21 mm Hg (mean +/- SD) compared to patients without nephropathy: 145 +/- 20 mm Hg (p < 0.05) and to healthy subjects: 133 +/- 19 mm Hg (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Size- and charge selectivity of glomerular filtration in Type 1 (insulin-dependent) diabetic patients with and without albuminuria.

Albuminuria is the first clinical event in the development of diabetic nephropathy. We assessed glomerular charge- and size selectivity in 51 patients with Type 1 (insulin-dependent) diabetes mellitus of juvenile onset and 11 healthy individuals. Patients were allocated to five groups. The urinary albumin excretion rate was normal in group D1; 30-100 mg/24 h in group D2; 101-300 mg/24 h in group D3 and greater than 300 mg/24 h in groups D4 and D5. Group D5 had elevated serum creatinine (above 110 mumol/l). Glomerular filtration rate and renal plasma flow were determined by constant infusion techniques and tubular protein reabsorption by excretion of beta 2-microglobulin. Charge selectivity was estimated from the IgG/IgG4 selectivity index. Size selectivity was measured by dextran clearance. Dextran was measured by refractive index detection after fractionation (2 A fractions in the range 26-64 A) by size exclusion chromatography. IgG/IgG4 selectivity index was significantly decreased in patients with albuminuria (p < 0.001). The drop in IgG/IgG4 selectivity index was found in patients with minimal albuminuria (D2) and was not accompanied by any changes in tubular function or glomerular haemodynamics. Size selectivity was significantly altered only in patients with the most advanced nephropathy (D5) as reflected by an increase in the clearance of 62 A dextran (p < 0.04). We conclude that loss of glomerular charge selectivity precedes or accompanies the formation of new glomerular macromolecular pathways in the development of diabetic nephropathy.

Adult↗
PubMed1993

Diabetes mellitus induced inhibition of glucosaminyl N-deacetylase: effect of short-term blood glucose control in diabetic rats.

Inhibition of glucosaminyl N-deacetylase activity, a key enzyme in heparan sulphate sulphation, may be involved in the development of late diabetic vascular complications. We examined the effect of short- and long-term metabolic control on N-deacetylase activity in streptozotocin diabetic H and U rats. Spontaneously diabetic BB rats were included in parts of the study. Over a 3-week period blood glucose was maintained at predetermined levels (6-10 mmol/l or 10-20 mmol/l) by insulin treatment and then during the final 2 days rapidly reversed in half of each group. In the U rats, the hepatic N-deacetylase activity significantly decreased by 10-15% following short- and long-term poor metabolic control and the inhibition was entirely reversed by short-term good control. In the H rats a similar, not significant, effect was seen. BB rats in long-term poor control showed a 10% reduction in hepatic N-deacetylase activity (p = 0.003). Glomerular N-deacetylase activity was reduced in U rats after long-term poor control (p = 0.004) but not in H and BB rats. There was an overall correlation between urinary albumin excretion and glomerular N-deacetylase activity (r = -0.60, p < 0.0001). We conclude that diabetes-induced inhibition of hepatic N-deacetylase is not restricted to the streptozotocin diabetic model, and that short-term blood glucose control is of major importance. Genetic factors and tissue specificity influence the vulnerability of the enzyme. Finally, the study suggests an association between N-deacetylase activity and urinary albumin excretion.

Albuminuria↗
PubMed1993

Glucosaminyl N-deacetylase in cultured fibroblasts; comparison of patients with and without diabetic nephropathy, and identification of a possible mechanism for diabetes-induced N-deacetylase inhibition.

Impaired heparan sulphate biosynthesis through diabetes-induced inhibition of glucosaminyl N-deacetylase may have a central role in the development of diabetic nephropathy, and genetic differences in the vulnerability of the N-deacetylase could influence the risk of developing nephropathy. We studied N-deacetylase activity in fibroblast cultures from Type 1 (insulin-dependent) diabetic patients with (n = 14) or without (n = 13) diabetic nephropathy, together with non-diabetic control subjects (n = 7). No difference in N-deacetylase activity was found (p = 0.13), and no inhibition of N-deacetylase was found in cultures grown at 25 mmol/l glucose. N-deacetylase activity was inversely correlated to growth rate (r = -0.59, p = 0.0008), and in patients with nephropathy a negative correlation between HbA1C and fibroblast N-deacetylase activity (r = -0.72, p = 0.012) was found. Cell-cycle analysis revealed an increased fraction of S-phase cells in patients with nephropathy (28%(21-52%)) compared to healthy control subjects (17% (9-24%)), p = 0.0008, but not between patients with and without nephropathy (latter group 26%(11-43%)), p = 0.43. Forskolin, an activator of protein kinase A, specifically decreased N-deacetylase activity, whereas activation of protein kinase C produced a combined reduction in N-deacetylase activity and total protein synthesis. In conclusion, no constitutive defects in N-deacetylase activity were found in fibroblasts from these patients. Further studies should consider possible associations between fibroblast characteristics and pre-biopsy environmental parameters related to cellular memory phenomena. Finally, activation of protein kinase A provides a potential general pathway for regulating N-deacetylase activity.

Adult↗