A standardized meal stimulation test of the endocrine pancreas for early detection of pancreatic endocrine tumors in multiple endocrine neoplasia type 1 syndrome: five years experience.

Forty-nine members of 6 families with multiple endocrine neoplasia type 1 (MEN 1) were investigated with a standardized meal stimulation test to detect the presence of pancreatic endocrine tumors. Fifteen age-matched subjects and 4 patients with primary hyperparathyroidism also were studied. Serum pancreatic polypeptide (PP), gastrin, and insulin as well as plasma glucagon and somatostatin concentrations were determined before and during the test meal. Patients with demonstrable pancreatic endocrine tumors had significantly increased mean basal and peak serum PP (P less than 0.001) and gastrin (P less than 0.001) responses to the meal compared with healthy family members and normal subjects. Seven of 12 MEN 1 patients with parathyroid and pituitary disease but no demonstrable pancreatic endocrine tumors had exaggerated PP and/or gastrin responses to the meal; 4 of them developed pancreatic endocrine tumors, detected by abdominal computerized tomography, 0.5-4 yr later. None of the healthy members of the MEN 1 families or the patients with primary hyperparathyroidism had responses different from those of the normal subjects. Our experience with the meal stimulation test indicates that an elevated basal or exaggerated serum PP and/or gastrin response is an earlier sign of pancreatic involvement in the MEN 1 trait than is abdominal computerized tomography.

Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds.

A total of 80 individuals in 4 kindreds with multiple endocrine neoplasia type 1 (MEN 1) have been subjected to repeated biochemical screening during a 10-yr period with the principal aim being to analyze characteristics of the developing pancreatic lesion. Age at presentation of the MEN 1 trait averaged 18 yr in 7 previously unaffected individuals, and this effect of the screening procedure represented a lowering by almost 2 decades. Pancreatic endocrine involvement was recognized at a mean age of 25 yr and constituted the presenting lesion in a majority of the patients. A standardized meal test and basal values of serum pancreatic polypeptide, insulin, proinsulin, and gastrin were the most efficient markers for the pancreatic lesion and preceded signs of pancreatic tumors upon radiological examinations by a mean of 3.5 yr. A 75% penetrance of the islet cell disease and 90% for primary hyperparathyroidism within the affected individuals equalled the prevalences reported in autopsy studies. Two of the kindreds showed signs of intrafamilial homogeneity with respect to the profile of peptide excess (P less than 0.05) and considerable discrepancy in the malignant potential of the pancreatic lesions. The results of early detection and surgical intervention of the pancreatic tumors in MEN 1 suggested an impact on morbidity, while any effect on the mortality of these individuals remains to be clarified.

Continuous recording of muscle nerve sympathetic activity during percutaneous transluminal angioplasty in renovascular hypertension in man.

We have previously shown that during percutaneous transluminal renal angioplasty (PTRA) there is a transient increase in plasma renin activity (PRA) that is partly mediated by adrenergic beta-receptors. Despite a concomitant increase in plasma aldosterone, no increase in blood pressure occurred. The aim of this study was to record sympathetic outflow in man during PTRA as reflected by muscle nerve sympathetic activity and arterial plasma noradrenaline. Nine patients with hypertension and unilateral renal artery stenosis underwent PTRA by the Grüntzig technique and simultaneous microelectrode recording of muscle nerve sympathetic activity in the peroneal nerve. Blood pressure and heart rate were recorded and blood specimens were drawn for determination of noradrenaline and PRA. During total occlusion of the renal artery, muscle nerve sympathetic activity and the heart rate were unchanged. In the first 6 min after occlusion PRA increased transiently, but there was no significant change in muscle nerve sympathetic activity, arterial noradrenaline, heart rate or blood pressure. From 10 min after PTRA, muscle nerve sympathetic activity was significantly increased and after 40 min there was a significant increase in noradrenaline. The heart rate remained unchanged throughout the procedure, but the blood pressure decreased progressively and the diastolic blood pressure was significantly reduced at 40 min, indicating successful dilation. Despite activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, two strong pressor systems, the only circulatory reaction was a decrease in diastolic blood pressure. These findings indicate simultaneous activation of a potent depressor mechanism during PTRA.

Vascularization of the continuous human colonic cancer cell line LS 174 T deposited subcutaneously in nude rats.

The macro- and microvasculature of the human colonic cancer cell line LS 174 T, 2-8 weeks after subcutaneous deposition in both hind legs of congenitally athymic rats was investigated by light microscopy, angiography, and microvascular corrosion casting with analysis in a scanning electron microscope. The tumour blood vessels were connected to branches of the femoral artery. Only the outer 200-500 micron of the tumour was extensively vascularized, with several concentric, incomplete layers of tortuous vessels, resembling onion skin. Light microscopy revealed necrosis and bleeding in the centre of the tumour, especially in the older tumours, which corresponded well to the central avascularity observed in the casts. There was an increase in venular and capillary density and tortousity towards the tumour in the adjacent muscular fascia. It is concluded that the cell line LS 174 T grows invasively inwards and recruits its vessels from the nude rat host. The overall tumour vascular pattern was unorganized, suggesting limited control of new vessel formation. Extravasations of resin, which were encountered in all cast tumours, can be a rough indicator of enhanced vascular permeability.

Collateral circulation following repeated distal embolization of the hepatic artery in pigs.

The distal hepatic arteries of eight pigs were embolized weekly with nondegradable microparticles. Hepatic angiograms were obtained before and after each embolization. One week after the last embolization Microfil was injected into the arterial and portal vascular beds of the liver prior to sacrifice. This study reveals that extensive collateral circulation develops after both primary and repeat embolization. After a third embolization in four of the pigs, the hepatic arterial circulation was almost totally abolished in two pigs with resulting extensive liver necrosis. An intact portal circulation is not sufficient to prevent infarction in dearterialized liver parenchyma.

Enhanced drug retention in VX2 tumors by use of degradable starch microspheres.

Twenty-nine rabbits with 12- to 14-day-old VX2 tumors in the hind leg were injected intraarterially with technetium-99m (99mTc) DTPA and various combinations of biodegradable starch microspheres, Spherex (Pharmacia, Sweden), to evaluate the efficacy of the microspheres in enhancing tumor retention of 99mTc DTPA. A gamma camera and nuclear medicine computer were used to generate time activity curves of 99mTc DTPA concentration in the tumors. Blood flow to the tumor and various muscles was also measured at intervals by left ventricular injection of 15 micron radiolabeled plastic microspheres. Ninety minutes following the administration of 99mTc DTPA, specimens from the tumor, plasma and different muscles were counted in a NaI well counter connected to a multichannel analyzer. When biodegradable microspheres mixed with 99mTc DTPA were injected and followed by a slow infusion of plain starch microspheres, the 99mTc DTPA was retained in the tumor at concentrations up to 11 times that seen when 99mTc DTPA alone was injected; the corresponding biological half-time was 13 times longer than control values. Additionally, the degree of drug retention was inversely related to blood flow, with retention increasing as blood flow decreased. The results have possible applications to the use of biodegradable microspheres in the intraarterial delivery of chemotherapeutic agents to solid tumors.

Spontaneous variations in renal vein renin activity in man.

The spontaneous variations in renal vein renin activity (RVRA) and in peripheral vein renin activity (PVRA) were studied in one normotensive and nine hypertensive patients. Eight of the hypertensive patients had renal artery stenosis on one or both sides. Blood samples were drawn simultaneously from the two renal veins and from a peripheral vein every fifth or tenth minute for one hour. Plasma renin activity (PRA) was measured by radioimmunoassay. The precision of the PRA assay, expressed as coefficient of variation, was related to the PRA level. A large intra-individual variations was found in RVRA, the RVRA ratio and PVRA even in patients with unilateral renovascular hypertension. The intra-individual variation could not be explained by specimen collection error or by error of the assay procedure. The variation seems to be reflect a biological fluctuation. The clinical implication of these findings is that repeated, simultaneous collection from the two renal veins, avoidance of factors known to decrease renin secretion. and consideration of the relation between the RVRA ratio and RVRA level are of importance in the preoperative evaluation of patients with renal artery stenosis.

Arterial vasoconstriction: a possible pathogenetic factor in the process of atherosclerosis.

The nutritional supply of arteries with a wall thickness of more than 0.5 mm takes place partly by diffusion from the lumen of the artery and partly from the adventitia through the vasa vasorum. The diffusion capacity is partially dependent upon the wall thickness and the intravascular pressure. During vasoconstriction both the wall thickness and the work of the muscle cells of the media are increased. The metabolic demands thus become greater at the same time as the nutritional supply deteriorates. Arterial vasoconstriction may cause a change in metabolism in the media, leading to a primary lesion in the arterial wall.

Hemobilia in childhood.

During a 10-year period we have encountered three cases of hemobilia among children after blunt abdominal trauma. All patients had the classical symptoms with varying degrees of severity. One of the patients, a 5-year-old boy, had several episodes of severe gastrointestinal bleeding, abdominal pain, and jaundice during a 2-month period. He was treated with selective arterial embolization of the left hepatic artery. The symptoms ceased instantly, and the patient has remained healthy during an observation period of more than 2 years. In cases of hemobilia, selective arterial embolization is a safe method with no serious complications. Arterial collaterals develop very quickly and the risk of liver dysfunction is small. We suggest that embolization of hepatic arteries may be the treatment of choice even in small children with hemobilia.

Multiple aneurysms of visceral arteries in a child with polyarteritis nodosa.

A 9-yr-old boy with polyarteritis nodosa presented a ruptured ileocolic arterial aneurysm that was resected and ligated at emergency operation. After angiographic examination showing multiple aneurysms of visceral arteries the inferior mesenteric and the common hepatic arteries were also ligated. One year postoperatively and on steroid medication the child is symptomfree with normal laboratory data.

Duplex ultrasound scanning for diagnosis of aortoiliac and femoropopliteal arterial disease.

Forty patients with symptomatic aortoiliac and/or femoropopliteal occlusive arterial disease subjected to angiography were studied with duplex ultrasonography. The duplex scanning of the aortic, iliac, femoral and popliteal segments had a sensitivity of 93% in detecting significant stenoses and a specificity of 91%. The positive and negative predictive values were 75% and 98%, respectively. The sensitivity was relatively low in low-flow segments distal to total occlusions especially in patients with severe iliac disease and multiple distal femoropopliteal lesions. The results demonstrate the reliability of duplex scanning in detecting aortoiliac and femoropopliteal lesions.

Segmental arterial spasm in patients with total brain infarction.

An arteriographic investigation has shown that segmental spasm occurs in a relatively high frequency of patients with total brain infarction (12 of 30), and if spasm at the origin of arterial branches is included, the frequency is still higher (19 of 30). The phenomenon is possibly a sign of changed sympathetic tone, the pathophysiological significance of which is discussed.

Ureteral reflux and ileal conduit pressure following diversion with a reflux-preventing technique.

Ileal conduit urinary diversion was performed with an antireflux technique, with nippling of the ureters into the segment, in 63 patients. The patients were then followed up for 52 +/- 25 months concerning urographic findings, infections and kidney function. Ureteroileal stenosis developed in 3 of 122 ureters and was surgically corrected. Roentgenologic examination for ureteral reflux was performed about a year postoperatively, and pressure measurements were made in the ileal segment. Reflux of contrast medium was seen in 48 ureters at pressure 51 +/- 30 mm Hg. When no reflux was seen, the maximum infusion pressure was 62 +/- 34 mm Hg. The basal pressure (preceding contrast infusion) was 24 +/- 29 mm Hg. Regular contraction waves with pressure rise in the ileal segment were registered, with duration 10-30 seconds. The study showed no connection between ureteral reflux and pressure in the ileal segment. Complications associated with the antireflux operating technique were few.

Rupture of an abdominal aortic aneurysm into the vena cava.

Aortic abdominal aneurysm combined with aorto-caval fistula is a rare condition with a high mortality. We discuss here the sympatomatology and treatment of one such patient.

Influence of sympathetic nerve activity on renal haemodynamics and release of renin. A preliminary communication.

The role of the sympathetic nerve system is still unknown in different types of hypertension. The procedure used in the evaluation of suspect renovascular hypertension has been revised in such a way that renal blood flow, renal arterial blood pressure and plasma renin activity in renal vein could be determined prior to and after splanchnic blockade. A new divice-videovolumeter-has been used to investigate the blood flow. Some preliminary data are given.

Age related changes in tumor vascularity. Angiography and vascular casts of the VX2 tumor in the rabbit hind leg.

VX2 tumors in the rabbit hind leg were investigated at one, two and three weeks of age. Angiograms were compared with vascular casts. The tumors grew rapidly the first two weeks of age. Large variations in vascularity were noted between tumors of different ages. With increasing age arteriovenous shunts at the tumor periphery and areas of avascularity or necrosis in the tumor center increased in size. Possible reasons for tumor necrosis are increased tissue pressure, anoxia caused by arteriovenous shunts and elevation in venous pressure. The natural history of the VX2 tumor must be considered in every experimental study of the effect of any treatment.

Liver necrosis after hepatic dearterialization in pigs.

In nine pigs, the livers were dearterialized by a combination of distal occlusion of the hepatic artery with Ivalon (polyvinyl alcohol foam) particles of 150-250 mu and proximal occlusion of the common hepatic artery with Gianturco coils. Necrosis of at least 90% of the liver developed in eight pigs. One pig with less extensive liver necrosis had developed an effective collateral circulation to a large part of the liver. Patency of the portal venous system did not prevent extensive infarction of dearterialized liver tissue.