Direct puncture and sclerotherapy with sotradecol ((r)) . Orbital lymphatic malformations.

SUMMARY: We evaluated sclerotherapy in the treatment of orbital lymphatic malformations. Six consecutive patients with unilateral orbital cystic masses and recurrent episodes of orbital swelling were included in this retrospective study. All have been treated with percutaneous puncture and injection of Sotradecol (sodium tetredecyl sulphate) under radiographic guidance, on one or more occasions. Reduction of orbital mass volume was documented clinically and radiologically within a few weeks in all cases. There was total regression of proptosis in three instances. There were no immediate complications. One subject suffered a presumably coincidental orbital hemorrhage two weeks after treatment. Follow-up times ranged between six months and four years. Sotradecol sclerotherapy appears to be a useful adjunct to the therapeutic arsenal for orbitallymphatic malformations.

Percutaneous sclerotherapy of venous malformations of the head and neck using sodium tetradecyl sulphate (sotradecol).

Thirty-eight patients with venous malformations of the face, neck, and tongue underwent percutaneous sclerotherapy with direct puncture and instillation of sodium tetradecyl sulphate (Sotradecol) (33-67% solution, mixed with contrast material) into the lesions. Each patient underwent from one to seven treatment sessions (mean 2.2), followed by reconstructive surgery in three cases. Of the 34 patients who responded to the follow-up questionnaire, the late results were excellent or good in 23 patients (68%), moderate in eight, unchanged in three, and were worse in one. Compared with our previous experience of embolisation of such malformations with ethanol, the results with Sotradecol were slightly worse. There was one serious complication, unilateral loss of vision in a patient with a large malformation that extended to the orbit. In conclusion, percutaneous sclerotherapy with Sotradecol is effective treatment for venous malformations of the head and neck. Careful planning is essential to reduce the risks of the treatment.

Direct puncture of large arteriovenous malformations in head and neck for embolisation and subsequent reconstructive surgery.

Five patients with large arteriovenous malformations (AVM) of the head and neck, which were too large or inconveniently placed for operation alone, were treated by embolisation after direct puncture; two of them were subsequently operated upon. They all recovered without complications. Embolisation of the nidus and subsequent operation is a good alternative for the treatment of large AVM. Ligating the supplying arteries is not a treatment. If the arterial routes to the nidus have previously been closed by ligatures selective catheterisation is impossible, though direct puncture of the nidus is a possibility. The nidus of the AVM can then be obliterated by embolisation either as a treatment, or as a preoperative procedure.

Effect of antihypertensive treatment on kidney function in diabetic nephropathy.

The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin dependent diabetics (mean age 30). During the mean pretreatment period of 32 (range 23-66) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 72 (range 32-91) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mm Hg to 129/84 mm Hg and albuminuria decreased from 1038 micrograms/min to 504 micrograms/min. The rate of decline in the glomerular filtration rate decreased from 0.89 (range 0.44-1.46) ml/min/month before treatment to 0.22 (range 0.01-0.40) ml/min/month during treatment. The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment (greater than or equal to 6 years). One patient died from acute myocardial infarction (glomerular filtration rate 46 ml/min/1.74 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.

Fabrication of microballoons for interventional neuroradiology: preliminary report.

A simple and inexpensive method of making latex microballoons for neuroradiologic procedures is described. The balloons have been tested in experimental animals and used in human clinical procedures. Preliminary experience and results are presented.

Incipient nephropathy in type 1 (insulin-dependent) diabetes.

Patients with Type 1 (insulin-dependent) diabetes without proteinuria were studied to define those patients who will later develop persistent proteinuria (more than 0.5 g protein/24 h). Two investigations were performed; 71 patients were studied longitudinally for 6 years and another 227 patients were studied cross-sectionally. All were less than 50 years of age and had developed diabetes before the age of 40 years. At entry into the study they had no proteinuria (Albustix method), had normal blood pressure and urinary albumin excretion rates less than 200 micrograms/min (normal less than or equal to 20 micrograms/min). The best predictor of persistent proteinuria or an albumin excretion rate greater than 200 micrograms/min was the initial urinary albumin excretion rate. During the longitudinal study, seven patients with an urinary albumin excretion rate of more than 70 micrograms/min at the start of the study developed persistent proteinuria or an albumin excretion rate greater than 200 micrograms/min. In contrast, only three out of the remaining 64 patients with urinary albumin excretion rate less than or equal to 70 micrograms/min developed urinary albumin excretion rate greater than 200 micrograms/min. Patients with an urinary albumin excretion rate greater than 70 micrograms/min are thus at risk of developing diabetic nephropathy. We designate this stage of renal involvement incipient nephropathy. Patients with incipient nephropathy were further characterized in the cross-sectional study. Compared with normoalbuminuric patients, patients with incipient nephropathy had increased systolic and diastolic blood pressure, but normal serum creatinine. The glomerular filtration rate was higher than normal in patients with incipient nephropathy though not different from that of normoalbuminuric patients.

Variations in renal threshold for glucose in Type 1 (insulin-dependent) diabetes mellitus.

The blood glucose/urinary glucose relationship was studied in 23 patients with Type 1 (insulin-dependent) diabetes. Glucose was infused intravenously in order to increase blood glucose concentration slowly and gradually. The renal threshold was recorded at the slightest trace of glycosuria and varied by a factor of 2 (from 6.0 to 14.3 mmol/l). The rise in blood glucose required to change the urinary output (0-1.1 mmol glucose/20 min) varied by a factor of 7 (1.1-7.6 mmol/l). The maximal rate of tubular glucose reabsorption varied by a factor of 2 (0.93-1.98 mmol/min). The renal threshold was negatively correlated with the creatinine clearance (r = -0.052, p less than 0.05), but was not correlated with diabetic control, age or duration of diabetes. The maximal rate of glucose reabsorption was negatively correlated with age (r = 0.47, p less than 0.05) and duration of diabetes (r = -0.54, p less than 0.05). In conclusion, urinary glucose excretion is dependent on both renal threshold and the splay and the slope of the blood glucose/urinary glucose excretion curve. Thus, the degree of glycosuria is of value as an index of diabetic control only when the blood glucose/urinary glucose relationship is known. The inverse correlation between renal threshold and creatinine clearance limits the usefulness of measuring glycosuria in patients with nephropathy.

Comparison of six assays for glycosylated haemoglobin determination.

To examine which glycosylated haemoglobin A components and which assays are the most useful in assessing long-term control in diabetic patients we have compared glycosylated haemoglobin concentrations in normal subjects and diabetic patients measured by six different methods, three chromatographic, a colorimetric, an isoelectric focusing and an agar gel electrochromatographic method. Despite the fact that the correlation between methods was high and the precision calculated from intra-assay variations acceptable, several differences in results were found. Thus Isolab columns determined lower values than other chromatographic methods and the unstable aldimine fraction interfered in agar gel electrochromatography. The increase in HbA1 in diabetics compared with normals was less than the corresponding increase in both HbA1c and total ketoamine bound glucose. This finding was consistent with the observation that the contribution of HbA1a + b fraction to HbA1 was constant at glucose concentrations above 10 mmol/l while a linear increase in these minor haemoglobins and consequently in HbA1 occurred at glucose concentrations below this level. We conclude that HbA1c' determined either by isoelectric focusing or ion exchange chromatography are the assays of choice for the determination of glycosylated haemoglobin in clinical routine.

Diabetic nephropathy and arterial hypertension. The effect of antihypertensive treatment.

Our longitudinal study of urinary albumin excretion rate in long-term insulin-dependent diabetics without proteinuria (negative albustix) suggests that early detection of patients at high and low risk of developing persistent proteinuria, i.e., diabetic nephropathy, is possible by using a sensitive method for albumin determination. Our prospective studies in young insulin-dependent diabetics with diabetic nephropathy show that the rate of decline in glomerular filtration rate (GFR) varies considerably, with a mean of 0.75 ml/min/mo and a range from 0.1 to 1.50 ml/min/mo, and that an increase in arterial blood pressure to a hypertensive level is an early feature; 43% of the patients had diastolic blood pressure greater than 100 mm Hg. Early and aggressive antihypertensive treatment reduces both albuminuria and the rate of decline in GFR in young patients with diabetic nephropathy.

Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy.

The effect of early aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in ten insulin-dependent diabetics (mean age 29 years). During the mean pretreatment period of 29 (range 23-38) months the glomerular filtration rate (GFR) decreased significantly and the urinary albumin excretion rate and arterial blood pressure rose significantly. During the 39 month (range 28-48) period of antihypertensive treatment with metoprolol, hydralazine, and frusemide (furosemide) or thiazide, arterial blood pressure fell from 144/97 mm Hg (mean of all pretreatment values) to 128/84 mm Hg (mean of all post-treatment values), urinary albumin excretion from 977 micrograms/min to 433 micrograms/min, and GFR from 80 to 62 ml/min/1 . 73 m2. The rate of decline in GFR decreased from 0.91 ml/min/month before treatment to 0.39 ml/min/month (range 0.08 to 0.68 ml/min/month) during treatment.

Diet versus average Danish food in insulin-dependent diabetes mellitus. An evaluation during treatment with an artificial betacell.

Ten randomly selected insulin-dependent diabetics with minimal betacell function were studied during treatment with an artificial betacell during two consecutive 24-hour periods. Patients were randomly served diabetic diet for one 24-hour period and average Danish food during the other 24-hour period. No significant (P greater than 0.05) difference was found between the mean blood glucose concentrations, nor insulin requirements on average Danish food compared to diet. However, the mean amplitude of glucose excursions was significantly higher on average Danish food than on diabetic diet (median 3.6 versus 2.7 mmol/l, P less than 0.05). Thus insulin-dependent patients not following their diabetes diet will show increased blood glucose fluctuations.

Glycosylated haemoglobin and steady-state mean blood glucose concentration in Type 1 (insulin-dependent) diabetes.

Since glucose control and glycosylated haemoglobin varies asyncroneously, we have studied the steady-state relationship between these two factors. In Type 1 (insulin-dependent) diabetic patients with a constant haemoglobin A1c during the preceding 2 years, 15 ambulatory blood glucose profiles during a 5-week period showed a constant glucose level and provided a precise estimate of the mean blood glucose concentration. In addition, we studied 15 non-diabetic subjects who provided three glucose profiles and had one haemoglobin A1c determination performed. A good correlation was found for a curvilinear relationship (haemoglobin A1c = 2.07 X mean blood glucose0.596, r = 0.98). This close relationship indicates that glycosylated haemoglobin is a valuable, but not very sensitive, index of glucose control.

Haemoglobin F and the assessment of glucose control by chromatographically determined HbA1c levels.

HbF and HbA1c-levels were determined in diabetic patients and non-diabetic controls to evaluate the influence of HbF on chromatographically determined HbA1c-levels. No difference in mean HbF was observed between controls and diabetic patients. However, in the combined material, women had a higher mean value (0.31%) than men (0.20%). Estimates of time average blood glucose concentrations (Cglc, mmol/l) were calculated from HbA1c-values in diabetic patients corrected for codetermined HbF. This correction resulted in a difference greater than 1 mmol/l in only 4% of diabetic men and 28% of diabetic women compared to estimates of Cglc from uncorrected HbA1c-results. We conclude, however, that the influence of HbF on chromatographically determined HbA1c-levels in most cases is of minor importance in assessing glucose control in diabetic patients.

Kidney function and size in diabetics before and during initial insulin treatment.

GFR, RPF, and kidney size were measured in nine young recently diagnosed insulin-dependent diabetics before (days 0) and 3 and 8 days after the beginning of the initial insulin treatment and in comparable control subjects. Kidney function was measured by a constant infusion technique using I-125-iothalamate and 131-I-hippuran. Kidney size was determined by means of ultrasound. Before insulin treatment elevated values for GFR (+44%, P less than 0.01), RPF (+18%, P less than 0.05), and kidney size (+29%, P less than 0.01) were found. Near-normal metabolic control was achieved in all patients using either multiple subcutaneous injections of insulin or an artificial betacell. GFR decreased from 160 +/- 9 SEM to 141 +/- 6 ml/min X 1.73 m2 (P less than 0.01) and further to 133 +/- 5 ml/min X 1.73 m2 (P less than 0.01, compared to day 0). Renal plasma flow was 601 +/- 33 and 588 +/- 44 ml x 1.73 m2 at days 0 and 3, respectively (NS) and decreased to 558 +/- 35 ml/min x 1.73 m2 at day 0 (P less than 0.01). By contrast no statistically significant changes in kidney volume were observed; the results on day 0, 3 and 8 were 145 +/- 7, 162 +/- 11 and 143 +/- 9 ml/1.73 m2, respectively. The present study demonstrates that kidney size and function are elevated at the onset of insulin-dependent diabetes. Near-normal metabolic control; for 8 days induces a reduction but not a complete normalization in kidney function. From the present observations it is suggested that the rapidly reversible part of the elevation in GFR cannot be explained by concomitant changes in kidney and glomerular size (morphological origin) but is probably due to a reduction in renal plasma flow and to a decreased transglomerular pressure (functional origin).

Synthesis of glycosylated haemoglobin in vivo.

The synthesis of glycosylated haemoglobins in vivo was measured during 24 h of controlled hyperglycaemia in seven insulin dependent diabetics. The mean blood glucose concentration was 22 mmol/l, while electrolytes and other metabolites were kept normal by infusion of 4-23 IU of insulin during hyperglycaemia. The study confirmed the velocity and magnitude of unstable HbAlc formation previously found in vitro. The stable HbAlc formed in 24 h was an average 0.006% of total haemoglobin/mmol glucose. This compares well with the rate of HbAlc synthesis reported in normal subjects using 59Fe-kinetic measurements, and is in accordance with the concept of slow changes in stable HbAlc with time and glucose concentration. To investigate the possibility that the rate of HbAlc synthesis varies with erythrocyte age, glycosylated haemoglobins were measured in erythrocyte fractions after density separation on Percoll-Albumin gradients. We found both in normal subjects and in insulin treated diabetics that the 5% least dense cells contained 70%-80% of whole blood HbAlc. Assuming the least dense cells to be the youngest erythrocytes, this observation is inconsistent with a slow linear increase in HbAlc. Similar results were obtained in six newly diagnosed insulin dependent diabetic patients both before and after the first 30 days of insulin treatment, even though a marked decrease in young cell HbAlc would be expected with the improved glucose control observed. We therefore conclude that density separation of erythrocytes is an inadequate technique to study age related HbAlc synthesis.

An artificial betacell: assessment of the glucose analyser, infusion system and optimization of constants for the algorithms.

The glucose analyser and insulin infusion modules of the Biostator were tested. The infusion system was reliable since more than 99% of the computed volume of insulin solution was delivered by the infusion pump at infusion rates above 1/100 of maximum, and no insulin was adsorbed onto infusion bags or tubing. Blood glucose results from the Biostator were compared with routine laboratory methods during long-term feedback control. Both slope (0.73) and scatter (r=0.87) around the regression line were unsatisfactory when the recommended calibration procedure was used. Tests in fasting non-diabetic subjects showed a significant correlation between the variation in Biostator glucose read-out and the plasma protein concentration in the detector outflow. In diabetics the ratio between Biostator glucose read-out and laboratory glucose determinations declined significantly with time. These observations led to the introduction of a standardization procedure based on externally determined blood glucose concentrations. During long-term feedback experiments in diabetics this procedure resulted in a significant increase in slope (0.84) but no improvement in scatter around the regression line. Repeated OGTTs revealed a set of constants for the algorithms, which enabled normal glucose tolerance to be achieved with smaller amounts of insulin.