Risk factors for ischaemic stroke in young Greenlanders.

INTRODUCTION: Contrary to a widely held belief, ischaemic cerebral infarction is not a rare disease in Greenland, as shown recently by our institution. We report data on some of the known risk factors in patients below 60 years of age with ischaemic stroke. METHOD: Retrospective data collection and review of charts from Greenlandic patients from all of Greenland admitted to the central hospital, Dronning Ingrids Hospital in Nuuk, in the years 2001 and 2002. RESULTS: A total of 37 patients below 60 years of age were discharged with a diagnosis of cerebral infarction. All had a CT, which showed infarction in 32. Five were reported normal, and the diagnosis of infarction rested on the absence of haemorrhage combined with long-standing, major neurological defect. Median age of the group was 54 years. Fifteen (40%) were women, thirty (81%) were smokers. Nine (24%) had hypertension. Two had diabetes, one had atrial fibrillation, and one had dilated cardiomyopathy. Two had significant carotid atherosclerosis diagnosed by duplex ultrasound. Of the rest, fifteen had transoesophageal echocardiography done, thirteen of which showed atherosclerotic changes. The cholesterol levels showed relatively high HDL levels. CONCLUSION: Ischaemic stroke is a common disease in young Greenlanders and seems to be associated with atherosclerosis with smoking as the only outstanding risk factor--though not more common than in the general population.

Incidence of myocardial and cerebral infarction in Nuuk, Greenland.

INTRODUCTION: Myocardial and cerebral infarction are held to be rare among the Inuit, whereas cerebral haemorrhage is thought to be frequent. Recent studies have questioned these beliefs. We report data form our institution. METHOD: Retrospective data collection and review of all charts from Greenlandic patients from the Nuuk area admitted to the city hospital, Dronning Ingrids Hospital, from 1999 to 2002. RESULTS: A total of 8 patients with myocardial infarction were found, median age 70 years, 4 with ST elevation MI and 4 with non-ST elevation MI. Two of the former had thrombolysis. Thirty-five patients were admitted with stroke, excluding subarachnoid haemorrhage, median age 65 years. Of these, twenty-nine had a CT. Five scans were reported as being normal, one patient had an intracerebral haemorrhage and twenty-three had cerebral infarctions. Six had no CT. One of these was admitted comatose and died without regaining consciousness, the rest were minor strokes in patients over 70. CONCLUSION: Myocardial infarction is a rare disease in Greenlanders, whereas stroke is four times as frequent. The overwhelming majority of strokes are infarctions, whereas intracerebral haemorrhage seems to account only for a small minority.

Development of insulin antibodies, metabolic control and B-cell function in newly diagnosed insulin dependent diabetic children treated with monocomponent human insulin or monocomponent porcine insulin.

One hundred and thirty eight patients participated in a two-year randomized, double-blind multicentre trial to compare monocomponent human insulin and porcine insulin in the treatment of newly diagnosed insulin dependent diabetic children with respect to development of insulin antibodies, metabolic control and B-cell function. There was no difference between the two patient groups throughout treatment either in the level of IgG insulin binding or the percentage of patients with insulin antibodies (IgG-insulin greater than 0.012 U/l). However, the estimated mean of log insulin binding values in the antibody positive patients alone was significantly lower (p less than 0.05) in the human insulin treated group at all times apart from 1 and 18 months (e.g., human insulin group at one and two years: 0.104 and 0.152 U/l, porcine insulin group at one and two years: 0.162 and 0.212 U/l). The insulin antibodies in both patient groups bound equivalent amounts of human and porcine insulin tracer. Metabolic control, insulin dosage and B-cell function in the two treatment groups were similar throughout the treatment period. It is concluded that in newly diagnosed insulin dependent diabetic children monocomponent human insulin is slightly less immunogenic than monocomponent porcine insulin, and equally effective in overall metabolic control.

The effect of buflomedil in diabetic retinopathy estimated by ocular fluorophotometry.

Tissue hypoxia is thought to be one of the possible factors involved in the etiology of diabetic retinopathy. Buflomedil has been reported to improve microvascular perfusion with a secondary increase in tissue oxygen pressure and may therefore be of interest in the study of diabetic retinopathy. We investigated 10 males with insulin-dependent diabetes and non-proliferative retinopathy, aged 24-46 with a duration of diabetes of 5-31 years. Buflomedil, 600 mg daily, or placebo was given for 4 weeks in a randomized, double-blind cross-over design, with a one-week washout in between. Patients were studied initially and at the end of each of the three periods. Ocular fluorophotometry was performed at each visit and a penetration index (PI) calculated by dividing the ocular measurements with the preceding average free fluorescein concentration. There was a slight, but significant decrease in the PI of the posterior vitreous while on buflomedil, from 10.6 +/- 13.4 (mean +/- SD) to 8.8 +/- 9.6 10(-4), p less than 0.05. No measurable changes were found in metabolic control as estimated by HbA1, and no side effects were observed. That the drug may act by increasing blood flow, was illustrated by measurements on capillary blood, where pH increased (7.43 +/- 0.01 to 7.45 +/- 0.01, p less than 0.05) and pCO2 decreased (5.48 +/- 0.4 to 5.15 +/- 0.24 kPa, p less than 0.05). Buflomedil may reduce the permeability of the posterior ocular barriers in diabetic retinopathy.

Microscopic appearance of the esophageal mucosa in a consecutive series of patients submitted to upper endoscopy. Correlation with gastroesophageal reflux symptoms and macroscopic findings.

The histologic finding of basal-layer hyperplasia and papillosis as consequences of gastroesophageal reflux still constitute an area of controversy. Consequently, a prospective study of symptoms and endoscopy and biopsy interpretation was undertaken in 200 patients consecutively submitted to upper endoscopy, whereof 12 were excluded. Complete agreement among all three variables was found in half of the patients and harmony between two of the variables in one fourth. In the last fourth the outcome was positive in one variable only, equally distributed among the symptoms, endoscopy, and histology. It is concluded that histology is of considerable value in gastroesophageal reflux disease.

Serum amylase during recovery from diabetic ketoacidosis.

To elucidate the mechanism of the hyperamylasaemia which is often found in diabetic ketoacidosis, 9 patients who were admitted in this disease state were studied. Blood samples were taken every 4 hours for the first 24 hours and thereafter daily for 7 days. Serum amylase concentration increased gradually in all patients, from 256 (65-1155) U/1 at the initial sampling to a maximum of 1160 (210-2670) U/1 20-24 hours later (p. greater than 0.01), median values with 95% confidence limits. Simultaneously, plasma inorganic phosphate concentrations decreased from a median value of 1.35 mmol/l to 0.45 mmol/l (p less than 0.01), and a significant negative correlation was found between the changes in these parameters in 5 patients. Isoenzyme analysis in 8 of the patients showed that hyperamylasaemia was of the "salivary type" in two and of the "pancreatic type" in two. None of the patients had clinical signs of pancreatitis. It is concluded that in diabetic ketoacidosis, the increase in serum amylase concentration observed in all patients is closely related to the action of insulin in the majority of these, and some possible mechanisms are discussed.

Ocular fluorophotometry in insulin-treated diabetic patients with and without retinopathy.

To look for possible determinators of the pathological readings of vitreous fluorophotometry in diabetes reported by other groups, we studied 32 insulin-treated patients, 22 of whom had fluorescein angiograms without pathological changes, while 10 had background retinopathy. 14 healthy subjects matched for age and blood pressure served as controls. Sodium fluorescein, 17 mg/kg body weight, was injected intravenously and ocular fluorophotometry performed 60 and 120 minutes later. Blood drawn 5, 45 and 120 minutes after the injection was assayed for total and ultrafiltrable fluorescein and the intraocular readings corrected for average preceding free plasma fluorescein. Patients without retinopathy did not differ from controls in any intraocular measure, while patients with retinopathy showed significantly increased readings in the posterior (60 min: 12 +/- 7 vs. 6 +/- 4, p less than 0.01, 120 min: 26 +/- 35 vs. 11 +/- 5, p less than 0.05) and middle vitreous (60 min: 6 +/- 3 vs. 3 +/- 3, p less than 0.001, 120 min: 11 +/- 5 vs. 8 +/- 5, p less than 0.01 (X 10(-9) g/ml fluorescein, mean +/- SD)). No significant relations to systolic or diastolic blood pressure, blood glucose, hemoglobin Alc or serum creatinine were found in any of the diabetic groups. Re-examination of 7 patients 4-14 days later in a non-fasting state showed no significant changes.

Some aspects of the pharmacokinetics of fluorescein in normal and in diabetic subjects.

A method for measuring the free fraction of fluorescein in plasma by ultrafiltration is tested. The coefficient of variation is 3%. Changes in pH and temperature from in vivo conditions at 37 degrees C to in vitro conditions are slight (less than 6%) and tend to minimize each other. To study the pharmacokinetics of fluorescein, 25 control subjects and 38 insulin-treated diabetics were examined after an intravenous injection of sodium fluorescein, 17 mg/kg body weight. 5, 45 and 120 min later, free fluorescein was significantly lower in the diabetics (5 min: 2.4 +/- 0.5 vs. 2.1 +/- 1.0, 45 min: 0.62 +/- 0.13 vs. 0.52 +/- 0.14, 120 min: 0.27 +/- 0.07 vs. 0.17 +/- 0.07 X 10(-5) g/ml, p less than 0.01 (mean +/- SD)). The renal excretion of fluorescein is reflected in a positive relation between serum creatinine and total plasma fluorescein at 45 and 120 minutes in the group of diabetics (Spearmans rho = 0.52, p = 0.04 and 0.53, p = 0.08, respectively).

Some methodological problems in ocular fluorophotometry.

Facing conflicting results from centers working with vitreous fluorophotometry, we performed a series of methodological studies of the technique preceding clinical studies. A major problem is the resolution power of the system. This is predicted to be dependent on the size of the fiberoptic probe, the slit width and angle between incident and detecting light beam, which is shown to be true in experiments with glass cuvettes and in studies of the eyes of 10 healthy volunteers. In the in vivo studies, variations of slit height could also influence readings. The selection of appropriate filters is important to reduce reflexes and autofluorescence of the ocular media, which otherwise must be accounted for.

Ocular fluorophotometry in normal subjects.

Leakage of fluorescein to the vitreous has been reported in diabetes and systemic hypertension. We have done detailed studies in normal subjects to look for determinators of possible leakage in this population. Twenty-nine healthy males, aged 18-67 years, were studied in the morning after an overnight fast. Fluorescein 17 mg/kg body weight was injected intravenously and blood drawn 5, 10, 15, 30, 45, 75 and 120 minutes later for measurement of ultrafiltrable fluorescein. Ocular fluorophotometry was performed before, 60 and 120 min after the injection. Mean fluorescein (+/- SD) in the posterior vitreous was 8.1 (+/- 5.5), middle vitreous 4.7 (+/- 6.0) and aqueous 240 (+/- 142) ng/ml after 60 minutes. At 120 minutes, a significant increase to 12.2 (+/- 8.6), 9.4 (+/- 9.3) and 317 (+/- 139) ng/ml was found in the three regions, p less than 0.05. At 60 minutes, age related significantly to posterior and middle vitreous concentrations, Spearmans rho = 0.49 and 0.61, as well as to aqueous concentrations, rho = 0.51 (p less than 0.01). Blood pressure related only to aqueous concentrations, at 60 minutes, rho = 0.42, p less than 0.05. When the intraocular measurements were corrected for average preceding ultrafiltrable fluorescein, age remained significantly related only to vitreous readings and blood pressure to aqueous readings.

Relationship between glycosylation of haemoglobin and the duration of diabetes: a study during the third trimester of pregnancy.

The relationship between blood glucose and glycosylated haemoglobin (HbAlc) had been investigated during an 8 week period in 53 Type 1 (insulin-dependent) diabetic women studied during the third trimester of pregnancy. Blood glucose estimations (fasting and 2h post-prandially) were made an average of 41 times in each patient during this period and HbAlc was determined once at the end of the study. There was a significant correlation between both the mean blood glucose over the preceding 8 weeks and the standard deviation of the fasting blood glucose with HbAlc (r = 0.69, p less than 0.001; r = 0.46, p less than 0.001, respectively). A "glycosylation index" was calculated for each patient (HbAlc divided by the mean blood glucose value). There was a significant correlation between the "glycosylation index" and duration of diabetes (r = 0.68, p less than 0.001). In contrast, there was no correlation between red cell 2,3-diphosphoglycerate and HbAlc or "glycosylation index". These findings suggest that increasing duration of diabetes influences the post-translational formation of HbAlc and that isolated HbAlc values need to be interpreted with caution in the pregnant diabetic.

The effect of etidronate disodium (EHDP) on retinopathy in insulin-dependent diabetic patients.

In a randomized double-blind study the effect of etidronate disodium (EHDP) on retinopathy, plasma inorganic phosphate and blood oxygen transport was assessed in 26 insulin-dependent diabetic patients. Following 6 months of EHDP administration, plasma inorganic phosphate had increased significantly (1.48 vs 1.14 mmol/l; P less than 0.01). Red cell, 2,3-diphosphoglycerate concentration (16.9 vs 15.1 mumol/g Hb; P less than 0.01) and the haemoglobin-oxygen affinity measured by pO2 at 50% oxygen saturation (P50) had also increased significantly (27.5 vs 26.3 mmHg; P less than 0.01). No changes had occurred in mean blood glucose and haemoglobin A1c concentrations, indicating a comparable degree of glucose regulation. Following 6 months of EHDP administration an association was found between improvement in retinopathy and the increase in plasma inorganic phosphate.

Hemoglobin A1c determinations in diabetic pregnancy.

To investigate the relationship of hemoglobin A1c (HbA1c) to average blood glucose concentration and to birth weight of infants of diabetic mothers, HbA1c was determined in 42 consecutive insulin-dependent pregnant diabetic women in the third trimester. HbA1c correlated significantly to the average blood glucose levels in the preceding 8 wk (r = 0.73, P less than 0.001). No correlation was found between HbA1c and the relative birth weight ratio (RBWR) for all newborn infants. However, in the major subgroups of pregnancies, White class B and C without prognostically bad signs in pregnancy (PBSP), HbA1c in the third trimester significantly correlated to RBWR (r = 0.59, P less than 0.01). In a subgroup of six pregnant diabetic women in whom HbA1c and blood glucose concentrations frequently were determined from the 13th to the 33rd gestational week, a relationship between HbA1c and the average blood glucose concentration of the preceding 8 and 12 wk in the individual pregnant subject was established. In spite of this correlation, HbA1c was found to be a poor predictor of the average blood glucose concentration in the individual patient. This indicates that HbA1c cannot satisfactorily describe the degree of diabetes control without simultaneous determinations of blood glucose. HbA1c determinations were found to be of value as an additional indicator of the quality of regulation during ambulatory control in diabetic pregnancy because an increase in HbA1c suggested an impairment of diabetic control. The perinatal mortality and morbidity of the infants of diabetic mothers were satisfactory in this series, as only one perinatal death, one nonserious malformation, and two cases of mild respiratory distress syndrome occurred among the 43 infants.

Glycosylated hemoglobin in relation to rapid fluctuations in blood glucose in children with insulin-dependent diabetes: a comparison of methods with and without prior dialysis.

To evaluate the importance of dialysis in the determination of glycosylated hemoglobin (HbA1), we studied blood glucose and HbA1 in 38 insulin-dependent diabetic children during a morning fast and again 6 h postprandially. We used two methods to determine glycosylated hemoglobin: (1) the conventional macrocolumn method of Trivelli, which uses dialyzed hemolysate and (2) a commercially available microcolumn procedure, Isolab's Fast Hemoglobin Test System, which uses undialyzed blood samples. When the 6-h changes were assessed, the mean blood glucose had increased from 11.6 to 16.3 mmol/L (P less than 0.001). HbA1, determined by the microcolumn procedure simultaneously increased from 12.6% to 13.4% (P less than 0.001), and the increment in HbA1 correlated significantly with the increment in blood glucose (r = 0.62, P less than 0.001). HbA1 determined by the macrocolumn method increased slightly from 13.1% to 13.4% (P less than 0.01), and no correlation was present between the increment in blood glucose and HbA1 (r = -0.02, NS). When the microcolumn procedure was modified by employing dialyzed hemolysate, this method became unaffected by acute blood glucose variations. Therefore, dialysis in sample preparation appears to be important in minimizing the effect of acute changes in blood glucose on the level of glycohemoglobin. Methods in which dialyzed hemolysates are used may be more useful as an index of long-term glucose control.

Hemoglobin A1c as an indicator of long term blood glucose levels in diabetics with special reference to diabetic pregnancy.

Hemoglobin A1c in diabetics has been shown to be an index of average blood glucose levels in the preceding 1-2 months. We confirm this relationship in a group of 12 insulin-treated diabetics and extend it to 16 pregnant insulin-treated patients as well. Lower levels of HbA1c in pregnancy could be explained by better control. In an ongoing sequential study of 5 pregnant diabetics home-monitoring their blood glucose, we have an impression, that this relationship holds true for individual patients. If this is confirmed, the level of glycosylated hemoglobins in pregnancy may be used as a warning signal for deterioration of glucose control in out-patients.