Comparison of recurrence rate and hemodynamic effect among various technical approaches for ligations of great saphenous vein in treatment of varicose veins.

BACKGROUND: The aim of this study was to compare the recurrence rate and hemodynamic effect retrospectively among various technical approaches for ligations of the great saphenous vein in the treatment of primary varicose veins. PATIENTS AND METHODS: 455 limbs with primary uncomplicated great saphenous varicose veins, which underwent ligations of the great saphenous vein followed by sclerotherapy, were classified into 5 groups according to different ligation techniques. The recurrence rate and hemodynamic effect, evaluated by the photoplethysmographic technique, were compared among the 5 groups at one year intervals up to 5 years. RESULTS: The 3-ligation technique, in which the great saphenous vein was resected at the groin, thigh, and calf, showed a significantly lower recurrence rate at the 5-year follow-up. The recurrence rates were 27.7, 62.0, 58.5, and 91.9% in the 3-ligation group, 2-ligation group at the groin and thigh, 2-ligation group at the thigh and calf, and 1-ligation group at the thigh, respectively. A lower hemodynamic improvement was observed in the latter two groups. A significantly higher recurrence rate was shown even in the 3-ligation group, when all tributaries were not dissected at the sapheno-femoral junction (50.2 vs. 27.7%, p<0.01). CONCLUSIONS: The 3-ligation technique followed by sclerotherapy, which includes the resection of the great saphenous vein for as long as possible, and dissection of all tributaries at the groin, thigh, and calf, is one of the important choices of minimum invasive treatments for varicose veins, although this technique is not a fully alternative procedure to the stripping operation.

Effect of dietary fiber, glucomannan, on absorption of sulfonylurea in man.

In order to clarify whether a dietary fiber has any effect upon the intestinal absorption of sulfonylurea, changes in plasma concentration of glibenclamide were determined during a six-hour period in nine healthy volunteers who took 2.5 mg of glibenclamide together with a breakfast and 3.9 g of glucomannan in a form of konjac powder and were compared with those of the control experiment in which the same amount of the hypoglycemic agent was given without the dietary fiber. In the control, mean plasma glibenclamide level increased rapidly, reaching a peak at 60 min and decreased gradually thereafter, whereas an increase in plasma glibenclamide level was blunted in the test experiment, thus plasma concentration of glibenclamide being lower at 30, 60, 90 and 150 min compared with the corresponding value of the control (31.7 +/- 24.5 ng/ml vs 76.4 +/- 25.0 ng/ml at 30 min; 51.3 +/- 35.5 ng/ml vs 120.9 +/- 56.0 ng/ml at 60 min; 60.0 +/- 38.8 ng/ml vs 117.4 +/- 53.1 ng/ml at 90 min; 54.0 +/- 31.5 ng/ml vs 100.7 +/- 46.5 ng/ml at 150 min). Mean plasma glucose concentration was significantly lower at 30 min in the test experiment than in the control despite the lower level of plasma glibenclamide in the former. The results suggest that glucomannan may influence the intestinal absorption of glibenclamide. A dietary fiber must be prescribed in due consideration of these facts.

Changes in somatostatin release from perfused pancreas of streptozotocin-induced diabetic rats.

To clarify the mechanism of an increased response of diabetic D-cells to arginine, we studied the changes in responsiveness of pancreatic D-cell to this agent with the passage of time after the onset of diabetes and the effect of chronic insulin substitution on the altered D-cell function utilizing the perfused pancreas of streptozotocin diabetic rats. The magnitude of somatostatin (SRIF) response to arginine (10 mM) was progressively increased with the duration of diabetes. The integrated response of SRIF during a 20 min period of an arginine infusion one week after the injection of streptozotocin was not different from that in the normals, but it was increased by 240% at 8 weeks and by 390% at 15 weeks. The exaggerated pancreatic SRIF release observed in 8 week diabetic rats was partially ameliorated with the daily insulin replacement (15.0 +/- 1.0 units/kg of B.W.). This was accompanied by a partial recovery from growth failure. The integrated amount of SRIF secreted during an arginine-stimulated period (20 min) was inversely correlated with an increase in body weight during an 8 week period (r = -0.741, p less than 0.001). From these results, it might be concluded that the alteration in diabetic D-cell function may be related to the metabolic and hormonal abnormalities of diabetes, rather than insulin deficiency itself.

Failure of exogenous insulin to inhibit C-peptide release from the perfused rat pancreas.

In order to ascertain whether insulin secretion is inhibited by insulin per se, the effect of exogenous rat insulin on basal and stimulated rat C-peptide reactivity (CPR) release was studied in the isolated perfused rat pancreas. The pancreas was perfused with a medium containing 20 or 200 ng/ml of rat insulin for a 20 min equilibration period and successively for a 25 to 30 min test period during which time glucose (300 mg/100 ml), tolbutamide (500 micrograms/ml), glucagon (500 ng/ml) or arginine (10 mM) was added as a secretagogue. The concentration of glucose in the basal medium was 60 mg/100 ml. Exogenous insulin did not significantly suppress the basal CPR secretion, nor did it cause a suppression of the peak value or incremental area of CPR while the pancreas was stimulated, but it rather augmented them. No inhibitory effect of exogenous insulin on the basal or stimulated CPR release was noticed in the present study.

Half life of gastrointestinal glucagon-like immunoreactive materials.

The composition, half life and hyperglycemic action of the porcine gastrointestinal glucagon-like immunoreactive materials were examined. Glucagon immunoreactivity (GI) measured using specific antiglucagon serum was more abundunt in the extract from the gastric fundus than in the one from the small intestine. When the extract from the gastric fundus was injected in dogs, the half life (T1/2) of total glucagon-like immunoreactivity (total GLI) measured using nonspecific antiglucagon serum was 9.5 +/- 1.1 min (mean +/- SEM), which was longer than that of crystalline pancreatic glucagon, 3.4 +/- 0.2 min, but shorter than that of the extract from the small intestine, 15.9 +/- 1.3 min. On the other hand, T1/2 for GI from the gastric fundus was 5.1 +/- 0.9 min, which was not significantly different from that of crystalline pancreatic glucagon. Blood sugar levels were significantly increased from the basal by 25 +/- 4 mg/100 ml at 10 min and 19 +/- 4 mg/100 ml at 15 min following an injection of the extract from the gastric fundus, but such a change in blood sugar levels was not demonstrated when the extract from the small intestine was injected. These results suggest that GI of the gastric fundus is close to pancreatic glucagon in respect of its metabolism and hyperglycemic activity.

Effect of secretin on plasma insulin and glucagon in man.

To investigate the effect of physiological doses of secretin on pancreatic A and B cell functions, secretin was infused at a rate of 0.5, 1.0 and 2.0 clinical unit per kg body weight per hr into eight normal men for 30 min or 60 min after an over-night fast, and changes in plasma immunoreactive insulin (IRI) and glucagon immunoreactivity (GI) were measured while monitoring circulating secretin levels by a radioimmunoassay. During the infusion of secretin, the plasma immunoreactive secretin (IRS) levels rose to 140-390 pg/ml which was within a range of the physiological fluctuation in plasma secretin levels reported hitherto. No significant alteration of plasma IRI and GI levels could be demonstrated during these simulated physiologic infusions of secretin. These data suggest that, in humans, the physiological dose of secretin does not influence insulin and glucagon secretion from the pancreas in the basal state.

[Glucagon-releasing activity of xenopsin, neurotensin and substance P in the perfused rat pancreas (author's transl)].

It has been reported that Xenopsin, Neurotensin and Substance P change plasma glucagon and insulin levels when they are administered in vivo. In order to clarify whether these agents have a direct effect on glucagon and insulin secretion from the pancreas, the action of each substance was examined by using the rat pancreas perfusion technique. The results were as follows: The perfusion with 1 and 5 nmole/min of Xenopsin for ten minutes resulted in a significant but transient release within two minutes. Neurotensin did not show any stimulatory effect on glucagon release in the concentration of 1 or 5 nmole/min for ten minutes. However, Substance P lowered significantly the glucagon concentration in the perfusate in a similar concentration. None of these substances influenced significantly insulin release from the perfused pancreas. These findings suggest that the hyperglucagonemia caused by these three agents in vivo may not be attributed to the direct effect on the pancreatic A-cell.

Insulin releasing activity of gastrointestinal glucagon-like immunoreactive materials in perfused rat pancreas.

Insulin-releasing activity of porcine gastrointestinal glucagon-like immunoreactive materials purified by affinity chromatography was examined in the perfused rat pancreas. When glucose concentration of the perfusate was raised from 60 to 100 mg/dl, augmented insulin release was observed. The mean incremental area of immunoreactive insulin (sigma delta IRI) during the first 10 min thus observed was 19.07 +/- 3.76 ng/10 min. Pancreatic glucagon and the extract from the gastric fundus showed the enhancement of insulin release in this system when they were added to the perfusate at the rate of 100 ng/min for 5 min; delta IRI were 41.92 +/- 8.47 and 71.70 +/- 18.09 ng/10 min, respectively, which were significantly higher than that of 100 mg/dl of glucose alone. However, no significant difference in the insulinogenic activity was noticed between the extracts from the small intestine and the control. These results suggest that the extract from the gastric fundus has insulinogenic activity similar to that of pancreatic glucagon.

Failure of exogenous insulin to inhibit insulin secretion in man.

In order to explore whether or not the negative feedback mechanism of insulin per se on insulin secretion exists in man, changes in plasma C-peptide immunoreactivity (CPR), as an index of pancreatic B cells secretory function, were studied in 6 nonobese healthy volunteers in the presence of high circulating levels of exogenous insulin. 10% glucose was infused concurrently so as to maintain blood sugar at the basal level. The insulin-glucose infusion was maintained for 120 minutes, achieving mean plasma levels of 140-180 mu1/ml. After this period, the insulin infusion was continued at the same rate for an additional 10 minutes while the glucose was omitted. Despite the elevated level of circulating insulin, no significant change in plasma CPR concentration was observed so long as the blood sugar was maintained at the basal levels. Following cessation of the glucose infusion, the plasma CPR levels declined with a decrease in blood sugar level. Under the conditions of the present study, no inhibitory effect of exogenous insulin on the secretory function of the B cells was noticed.

The pancreatic alpha and beta cells responses to 1-arginine and insulin-induced hypoglycaemia in hyperthyroidism.

In order to assess the secretory capacity of the pancreatic alpha and beta cells in patients with hyperthyroidism, the plasma glucagon and insulin responses to 1-arginine and insulin-induced hypoglycaemia in 12 patients were compared with those in 6 normal subjects. The response of beta cell to hypoglycaemia was evaluated by measuring the decrease in plasma C-peptide immunoreactivity (CPR) level. There was a negligible rise in blood glucose and plasma insulin levels in the patients, whereas a significant increase occurred in normal subjects during the arginine infusion. Although no difference in the fasting plasma glucagon concentration between the two groups was found, 30 min after the beginning of the arginine infusion, the plasma glucagon levels rose to a peak of 252 +/- 35 pg/ml in the patients, a value significantly lower than 387 +/- 53 pg/ml in the normal subjects. The insulin-induced hypoglycaemia caused no significant difference in the peak values of plasma glucagon between the two groups. There was a sigificant difference in the peak values of plasma glucagon between the two groups; There was a significant fall in plasma CPR after the insulin injection in both groups but the per cent decrement was rather greater in the patients than in the normal subjects.

Effect of phenformin on the response of plasma intestinal glucagon-like immunoreactivity (GLI) to oral glucose in gastrectomized subjects.

The effect of phenformin (DBI) on the plasma intestinal glucagon-like immunoreactivity (GLI) and pancreatic glucagon (IRG) responses to oral and intravenous glucose loads were studied in 26 gastrectomized subjects, using a cross-reacting and an IRG-specific anti-serum. The drug produced no significant changes in fasting GLI and IRG levels. Thirty minutes after oral glucose alone, the total GLI level rose to a peak of 1.55 +/- 0.17 ng/ml in the untreated subjects and to a maximum level of 1.67 +/- 0.18 ng/ml in the DBI-pretreated subjects. However, the mean GLI levels obtained 120 and 180 min after oral glucose were significantly higher after treatment with DBI. The blood sugar and IRI responses to oral glucose were lowered significantly by DBI pretreatment. DBI did not alter the glucose, IRI, IRG and GLI response to intravenous glucose. These results suggest that the release of intestinal GLI is not related to the intestinal absorption of glucose.

Effect of an exposure to chloramine-T on the immunoreactivity of glucagon.

Various preparations of glucagon treated with chloramine-T under different conditions have been studied with respect to their immunoreactivity toward two different glucagon antisera; one specific for pancreatic glucagon and the other capable of reacting with enteroglucagon as well. The glucagon preparations exposed to chloramine-T for different periods reacted almost identically with the nonspecific antibody whether they were used as tracer or standard. On the contrary, treatment with chloramine-T under severe conditions led to reduced immunoreactivity toward the specific antibody. Inclusion of dimethyl sulfoxide (DMSO) in the chloramine-T reaction resulted in preservation of the immunoreactivity of the treated preparations. The cyanogen bromide cleaved-glucagon, (1-26) homoserine lactone, showed little cross-reactivity with the specific antibody whereas it reacted to a similar extent with the nonspecific antibody as natural glucagon did. Amino acid analysis of the hormone exposed to chloramine-T demonstrated that the methionine residue at position 27 in the glucagon molecule had been oxidized to methionine sulfoxide. In addition, tryptophan had also been affected. DMSO protected methionine and tryptophan from the oxidative action of chloramine-T. We postulate from these results that the change in the immunoreactivity toward the specific antibody of glucagon exposed to chloramine-T is mainly due to oxidation of the methionine residue at position 27 in the molecule. The usefulness of DMSO in the iodination process is also discussed.