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Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are multifactorial, chronic, disabling, and progressive diseases characterised by cyclical nature, alternating between active and quiescent states. While the aetiology of IBD is not fully understood, this complex of diseases involve a combination of factors including the genetic predisposition and changes in microbiome as well as environmental risk factors such as high-fat and low-fibre diets, reduced physical activity, air pollution and exposure to various toxins and drugs such as antibiotics. The prevalence of both IBD and obesity is increasing in parallel, undoubtedly proving the existing interactions between these risk factors common to both disorders to unravel poorly recognized cell signaling and molecular alterations leading to human IBD. Therefore, there is still a significant and unmet need for supportive and adjunctive therapy for IBD patients directed against the negative consequences of visceral obesity and bacterial dysbiosis. Among the alternative therapies, a moderate-intensity exercise can benefit the health and well-being of IBD patients and improve both the healing of human IBD and experimental animal colitis. Intestinal alkaline phosphatase (IAP) plays an essential role in the maintenance of intestinal homeostasis intestinal and the mechanism of mucosal defence. The administration of exogenous IAP could be recommended as a therapeutic strategy for the cure of diseases resulting from the intestinal barrier dysfunction such as IBD. Curcumin, a natural anti-inflammatory agent, which is capable of stimulating the synthesis of endogenous IAP, represents another alternative approach in the treatment of IBD. This review was designed to discuss potential "nonpharmacological" alternative and supplementary therapeutic approaches taking into account epidemiological and pathophysiological links between obesity and IBD, including changes in the functional parameters of the intestinal mucosa and alterations in the intestinal microbiome., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The purpose of the study was to evaluate the splanchnic extraction of tissue plasminogen activator (t-PA) in normal healthy fasting subjects after the injection of recombinant t-PA (rt-PA; Actilyse). In nine healthy volunteers (five male, four female), 21-29 years of age, the concentration of t-PA was determined in plasma samples taken simultaneously from a femoral artery and a large liver vein after a bolus injection (5, 10 or 20 mg) of rt-PA. The splanchnic plasma flow rate, the plasma volume, and the splanchnic extraction fraction of t-PA were determined. After the rt-PA injection, the measured arterial concentration of t-PA decreased from 36 750 to 45 pmol/l for t-PA antigen and from 50 700 to 17 pmol/l for active t-PA. The splanchnic extraction fraction decreased from 0.95 to 0.02 for t-PA antigen and from 0.78 to 0.08 (n = 3) for active t-PA. The extraction fraction was proportional to the arterial concentration of t-PA when the arterial concentration of t-PA was above about 300 pmol/l (both t-PA antigen and active t-PA). The median splanchnic plasma flow rate was 911 ml/min (range, 651-1149 ml/min). In the individual subject, the splanchnic plasma flow rate remained constant during the experimental period. The main conclusion of the study is that the splanchnic clearance and extraction fraction of t-PA, following an injection of rt-PA in the resting fasting steady state, depends on the arterial concentration of t-PA. The higher the arterial concentration of t-PA, the higher the extraction fraction of t-PA.

Using an invasive technique, we studied the mean transit time, the net quantitative turnover rate, and the sites of synthesis and catabolism of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in healthy young volunteers in the fasting, steady state. Blood was sampled simultaneously from a large hepatic vein, an artery and the inferior caval vein, while measuring the splanchnic plasma flow rate and the plasma volume. We found that the catabolism of active t-PA and t-PA antigen took place in the splanchnic circulation with net rates of 7.2 and 6.3 pmol/min, respectively. The extraction fraction and the mean transit time in the splanchnic circulation were, respectively, 0.63 and 5.6 min for active t-PA and 0.17 and 21 min for t-PA antigen. Active PAI-1 was synthesized in the splanchnic circulation at a rate of 890 IU/min and had a mean transit time of about 9.8 min. No net extraction of PAI-1 antigen took place in the splanchnic circulation. In conclusion, we demonstrated that active t-PA and t-PA antigen are catabolized and active PAI-1 produced in the splanchnic circulation in young healthy subjects during steady state. Furthermore, our data show that active t-PA was also eliminated outside the splanchnic region with a catabolism rate of about 8.4 pmol/min. No net complex formation could be demonstrated in the peripheral circulation. We therefore suggest that active t-PA is eliminated by a re-uptake in the endothelium in the peripheral vessels or in the lung circulation.

Objectives: An audit of treating femoro-crural bypass stenosis in the first instance by PTA., Design: Prospective clinical pilot study in consecutive patients., Materials: Prior to vascular bypass grafting all patients had critical ischaemia. Sixty-four PTA procedures in 50 grafts in 49 patients were carried out. Thirteen were in situ saphenous grafts, 16 were combined venous segments, 18 were combined PTFE and vein and three were PTFE only., Methods: Conventional cross-over or antegrade PTA, eventually combined with local thrombolytic therapy., Results: The nine-month assisted patency using PTA was 72%, following surgical repair in five cases after failed PTA the secondary patency was 86%. The amputation free survival rate was 88%. In 11 cases thrombosis was treated successfully with local thrombolysis. In two cases the balloon ruptured the native artery wall below the distal anastomosis with pseudoaneurysm formation. Six limbs were amputated during follow-up. The frequency of stenosis in combined grafts was significantly higher than in in situ vein grafts., Conclusion: Our results are comparable with surgery. About 600 hospital beds/days were saved. This shortened the time from the diagnosis of stenosis to therapy and shortened the waiting list for vascular surgery.

Purpose: Compare the recanalization rate of femoropopliteal occlusions between movable core wire guide (MG) and hydrophilic guidewire (HG)., Methods: Conventional PTA technique was used, followed by enclosed thrombolysis. The MG was used for all patients in the first 2 years, the HG in the following 2 years. Baseline characteristics were similar for the two groups of patients., Results: Recanalization of 124 femoropopliteal occlusions was attempted. Technical success was achieved with the MG in 45 of 59 procedures; 42 procedures were clinically successful. Using the HG, technical success was achieved in 35 of 65 procedures; clinical success was achieved in 35 of 65 procedures; clinical success was achieved in 29 cases (p < 0.0048). At 1-year follow-up, 32 extremities improved after treatment with MG and 22 extremities after treatment with HG (p < 0.035)., Conclusion: The results suggest that the MG should be the first choice in recanalization of femoropopliteal occlusions.

The authors measured the binding of indium-111-labeled recombinant tissue-type plasminogen activator (rt-PA) within the recanalized femoropopliteal segment after percutaneous transluminal angioplasty (PTA) and enclosed thrombolysis. In patients with long occlusions (n = 3), 91 micrograms of rt-PA was bound 1 hour after the procedure, and the half-time of the final washout curve averaged 114 hours. After PTA in patients with multiple stenoses (n = 6), 45 micrograms of rt-PA was bound, and the half-time averaged 32 hours. These values were significantly smaller than those in patients with occlusions (P < .01). In patients with a single stenosis (n = 4), 19 micrograms of rt-PA was bound, and the half-time averaged 5 hours. These values were significantly smaller than those in patients with multiple stenoses (P < .01). The progressive accumulation of rt-PA at the sites of PTA therapy is most likely related to increasing presence of fibrin with increasing lesion severity. Fibrin accumulation may be partly responsible for early failures after PTA in extensive lesions. Removal of this fibrin with enclosed thrombolysis might improve patency.

Segmentally enclosed thrombolysis (SET) was performed immediately following 34 percutaneous transluminal angioplasties (PTAs) for femoropopliteal occlusions. The dilated segment was sealed off with a double balloon catheter, and recombinant tissue plasminogen activator (rt-PA) 1 mg/ml and heparin 200 IU/ml were injected between the balloons. The catheter was removed after 30 min and heparin treatment was continued for 24 h. Alpha-2-antiplasmin was initially reduced by 13% and normalized 2 h after SET, indicating that only small amounts of free plasmin were liberated during thrombolysis. No clinically relevant changes in plasma fibrinogen occurred. Two puncture site hemorrhages did not coincide with the coagulopathy induced by SET. One-year patency was 80%. Early rethrombosis occurred in 9% versus 41% in our previous series on standard PTA for femoropopliteal occlusions (p less than 0.001). Therefore, SET is considered beneficial in reducing the incidence of early rethrombosis.

The outcome of percutaneous transluminal angioplasty (PTA) was evaluated for treatment of 87 limbs with femoropopliteal stenoses, including 55 short stenoses (2.4 +/- 1.6 cm, mean +/- SD), seven single long stenoses (10.4 +/- 2.0 cm), and 25 multifocal stenoses (2.1 +/- 1.6 cm), where two to four separate segments were dilated. Following 98% initial technical success, 3-year patency was 68% for single short stenoses, as opposed to 20% for long and multifocal stenoses (p = 0.05, logrank test). Antiplatelet therapy with acetylsalicyclic acid was not found to influence occurrence of restenosis. The study documents the poor PTA results for long and multifocal stenoses and suggests precautions to be taken during PTA in order to minimize the area of artery wall damage.

Removal of fibrin from the site of a newly dilated femoro-popliteal occlusion may be an attractive way of preventing rethrombosis. A double balloon catheter with a dilating tip balloon and an occlusive balloon 10, 15 or 20 cm approximately were introduced percutaneously. Following successful dilatation of femoro-popliteal occlusions, the balloons were inflated on both sides of the lesion. The dilated segment was then isolated from the circulation. Through a sideport between the balloons 5 mg of tissue type plasminogen activator and 1000 IU of heparin were installed within the segment for 30 min. The authors report the results of 53 technically successful dilatations of femoro-popliteal occlusions followed by enclosed thrombolysis. A 100% patency at 3 months was noted in 33 patients having one to three run-off arteries, and the one year patency was 90%. In 20 patients, with no infrapopliteal run-off artery, four rethrombosis occurred within 24 h, and the one year patency was 62%. This difference is significant. (Log rank test, Chi-square = 4.73, p less than 0.05). We conclude that enclosed thrombolysis prevents early reocclusion following PTA of femoro-popliteal occlusions provided that at least one infra-popliteal artery is patent.

Possible sources of error during long-term measurements of subcutaneous blood flow rate with the portable CdTe(Cl) detector system were ruled out in the present study. Local blood flow rates were recorded in the lower legs of normal human subjects by means of the 133Xe wash-out technique. A good correlation was found between the portable CdTe(Cl) and stationary NaI(Tl) detector systems both prior to (r = 0.88, P less than 0.0001) and after (r = 0.68, P = 0.07) day over night (12 h) measurements. Identical post-ischaemic reactive hyperaemia could be demonstrated by both detector systems 12 h after the application of the isotope depot. This indicates that blood flow rates and vascular reactivity can be measured over 12 h by the portable CdTe(Cl) detector. Identical results were obtained during the 12-h measurements performed with the portable CdTe(Cl) detector attached directly to the skin surface and with the detector elevated above the skin surface. Therefore, geometrical changes were without any influence on our measurements. We conclude that measurements of subcutaneous blood flow rates in the lower leg of human subjects can be performed under out-patients conditions by means of the 133Xe wash-out technique and portable CdTe(Cl) detectors. A skin area greater than or equal to 4 cm should be labelled by means of the atraumatic, epicutaneous labelling technique and the detector attached directly to the skin surface with a single layer of a 20-micron thick gas-tight Mylar membrane interposed between the skin surface and the detector. The investigation of the subcutaneous blood flow rate should not be initiated until at least 90 min after labelling.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred and thirty-seven consecutive percutaneous transluminal angioplasties (PTA) were performed for femoropopliteal vascular disease including 58 stenoses and 79 total occlusions. Nine occlusions could not be crossed with the guidewire, but in the remaining 128 the haemodynamic and clinical success as well as vascular patency were evaluated. The results were grouped into the following subsets: the indication for PTA, the severity of the vascular lesion, the crural run-off and the length of lesion. The results were in every respect poor with total occlusions when compared with stenoses. This was explained by a high incidence (41%) of rethrombosis within hours of dilatation. Early rethrombosis was seen with all lengths of occlusion (1-27 cm) with no statistically significant difference from other subsets. This study concludes that conventional PTA in femoropopliteal occlusions should be reserved for cases of limb salvage, preferably in patients who are technically inoperable. We suggest a new technique of segmentally enclosed thrombolysis to prevent early rethrombosis after PTA in femoropopliteal occlusions.

Patients with severe ischemia due to multi-level obstructions in the leg arteries both above and below the region were assessed preoperatively by intraarterial brachial and femoral artery pressure measurements. The systolic pressure drop along aorto-iliac obstructions was compared to the angiographic findings. A consistent pressure gradient was found in the various types of arterial occlusions. In patients with occlusion of both the aorta and the iliac arteries, the systolic pressure drop was about 60% (range, 50-78%, SD 9%). The various types of iliac artery occlusions resulted in quite uniform systolic pressure drops of about 50% (range 35-68%, SD 9%). In contrast, the systolic pressure drop along different types of iliac stenoses showed a wide variation, ranging from a minimal drop to about 60%. The degree of stenosis on the angiogram was correlated significantly with the pressure drop. Due to large variations, however, the angiographic information was found to be useless in the individual patient. No difference in the pressure drop was found between cases in which rich and poor collateral networks were visualized.

Regional venous plasma aldosterone concentrations were determined and assessed against concurrent arterial levels in 16 patients with primary aldosteronism. The results obtained by sampling from the left adrenal vein or the left renal vein allowed correct side prediction of the presupposed adenoma in each patient. The problems caused by intermittent secretion of aldosterone by the tumour and the importance of correct positioning of the catheter are emphasized. Repeated sampling and continuing reference to systemic, arterial aldosterone levels proved valuable.

Wash-out of 133xenon from a local depot in the subcutaneous adipose tissue in the forefoot was measured continuously during 24 hours on subsequent recordings in 51 feet (normal circulation: 10, intermittent claudication: 22 and ischaemic nocturnal rest pain: 19) with a mean time interval of 26 days (range: 3-90 days). The patients were studied under two different conditions. Firstly, during the day in the erect position, awake (sitting, standing and quiet walking) and secondly, during night hours in the supine position, asleep. The coefficient of variation of nocturnal adipose tissue blood flow was calculated to 10%, and for the ratio of blood flow from day to night to 5%. The method is thus considered apt as a monitor in the treatment of peripheral vascular disease, for example, surgery and medical therapy. As predominant source of error is the formation of oedema.

Percutaneous transluminal angioplasty was performed on 55 iliac and 31 femoropopliteal arteries in 71 patients with intermittent claudication (23 women, 48 men). The two-year patency rate was 80% after iliac and 41% after femoropopliteal angioplasty. In 17 femoropopliteal cases with lesions greater than or equal to 5 cm the 2-year patency rate was only 32%, but the corresponding figure for shorter lesions was 53%. Complicating haematoma appeared in 10% of the cases and the arterial state deteriorated in one patient. There was no distal embolization. Percutaneous transluminal angioplasty in intermittent claudication is indicated for all cases of occlusion or stenosis of the iliac artery and for occlusion or stenosis shorter than 5 cm of the superficial femoral or the popliteal artery.

The function of sympathetic vasoconstrictor fibres was studied in 18 patients with occlusive arterial disease of the legs and somatic neuropathy, as evidenced as an increased vibration perception threshold. Nine patients suffered from long-term diabetes mellitus. Sympathetic vasoconstrictor function was studied by the capability of the local sympathetic venoarteriolar reflex (Henriksen 1977) elicited by lowering the leg to induce an arteriolar constriction in subcutaneous tissue at the ankle level. Blood flow was measured by the local isotope washout technique. In only five patients with loss of vibration sense, abnormal vasoconstrictor function was found. In three of these patients, the abnormal response most likely could be ascribed to impaired function of the vascular smooth muscle cells. Neither in diabetics nor in non-diabetics could an abnormal vibration sense be taken as evidence for loss of sympathetic vasoconstrictor function. It is suggested that this is studied by a simple postural test as used in the present study.

Knowledge of the tissue to blood partition coefficient (lambda) is essential for calculation of the perfusion coefficient in a single tissue based on measurements of the washout of locally injected isotopes. No measurements of lambda for Xenon in subcutaneous tissue in the leg have been done in patients with occlusive arterial disease. In 12 patients with occlusive arterial disease in the legs lambda for Xenon was determined in subcutaneous tissue in the calf region and foot as the ratio between the washout rate constant of 131I-Antipyrine and 133Xe. A mixture of the two indicators was injected subcutaneously laterally on the calf and in the first interosseous space on the foot. The time until the curves followed a monoexponential course varied between 15 and 45 min in the calf and 5 and 45 min in the foot. The calculated lambda for Xe showed a great variance between individuals in calf as well as foot. Mean value was 3.7 ml X g-1 (range: 1 X 7-10 X 7) in the calf and 2 X 7 ml X g-1 (range: 1 X 2-4 X 9) in the foot. It is concluded that lambda measurements are necessary for determination of subcutaneous blood flow from 133Xe washout curves in these patients. Determination of lambda is especially important when comparisons are made between individuals.

The effect of temperature changes (36-40 degrees C) on the liver function was studied in the isolated perfused pig liver. When compared with control studies no effect was observed on lactate, glucose, bile flow, ATP and energy charge, and the recovery after the changes in temperature was complete. The only significant changes observed regarded the hepatic oxygen uptake and galactose elimination capacity. The increase of 1 degree C resulted in an increase in galactose elimination of 6%, corresponding to a Q10 of 1.98 (SEM 0.12) with an energy of activation of 48 kJ/mol (SEM 4.7). Oxygen uptake was linearly related to galactose elimination (1.75 mol for 1 mole change in galactose elimination). These results indicate that circulatory changes are unimportant within physiological temperature changes. It is concluded that temperature effects on galactose elimination are too small to warrant a correction when used as a clinical test of quantitative liver function.

Systolic blood pressures at toe and ankle were measured in 459 consecutive patients with occlusive arterial disease. Fifty-eight per cent had intermittent claudication with arterial disease of all degrees of severity. Seventeen per cent complained of rest pain having toe systolic pressures below 30 mmHg, half had arterial lesions proximal to the groin. None had diabetes. Fourteen per cent non-diabetic patients had chronic ulcerations on the foot with arterial lesions similar to those in patients with rest pain. Eleven per cent diabetic patients with chronic ulcerations had less pronounced occlusive arterial disease which was located distally on the legs. A classification in three groups is suggested: (1) ischemia only during exercise; (2) ischemia at rest with or without ulcerations: and (3) diabetics with chronic ulcerations.

The effects of hypoxaemia and ischaemia were compared in the perfused pig liver. Decreased hepatic oxygen uptake, galactose elimination, ATP phosphorylation and increased lactate output occurred when the oxygen supply was diminished below 55% of the mean of controls. Below the control limits for oxygen uptake and oxidative phosphorylation, the change in the above variables were correlated to the degree of hypoxia, with no quantitative differences regarding ischaemic or hypoxaemic hypoxia. Galactose elimination was correlated to the ATP concentration (r = 0.81). After 80 min of hypoxia almost complete recovery was seen. It can be inferred from the data that other factors than oxygen diffusion into the liver cells may limit oxidative metabolism. Long and severe hypoxia may be required before irreversible cellular damage occurs in the liver.

The vascular response in the lower extremities to 40 degrees head-up tilt was studied in 5 patients with occlusion of the superficial femoral artery and maturity onset diabetes mellitus with symptoms suggesting autonomic neuropathy. The pressure measurements were performed via catheters placed in the brachial artery, femoral artery and vein and popliteal artery and vein. Relative blood flow was calculated as the relative change in arterio-venous oxygen saturation. Absolute blood flow in the common femoral artery was measured by an indicator dilution technique. Resistance of the collateral arteries increased by 40% during head-up tilt compared with horizontal position. Total leg resistance increased by 24%. Vascular resistance did not change below the knee. Intra-arterial alpha-blockade abolished the increase of vascular constriction in the leg during head-up tilt indicating that alpha-adrenergic tone was present in limbs studied.

In a double-blind cross-over trial an oral thromboxane synthetase inhibitor (TSI) or placebo was given to 15 patients with severe foot ischaemia. After TSI therapy, rest pain remitted in nine out of 14 legs, while remission during placebo was seen in three out of 11 legs (NS). The ankle and toe systolic blood pressures remained constant during both study periods. Nocturnal adipose tissue blood flow in the forefoot was measured by the xenon wash-out method. A significant increase of the nocturnal perfusion rate constant during TSI therapy was found. A slight oedema developed during TSI therapy. This causes a change of the composition of the tissue under study and thus of lambda-xenon. The perfusion rate in the present study thus merely illustrates the latter and not a true increase in blood flow.

Two-plane angiography and direct segmental pressure measurements in the femoral and popliteal arteries and indirectly on the arm and ankle were performed in 101 limbs seeking to establish a relationship between angiographic assessment of the patency of the popliteal artery and the trifurcation vessels and the popliteal ankle pressure difference. When the tiberoperoneal trunk or the trifurcation vessels were occluded or more than 50% of the lumen was stenosed, the pressure difference exceeded 10 mmHg in 30/40 limbs (75%). When three, two, or only one of the tibial vessels were patent, the pressure difference exceeded 10 mmHg in 2/58 limbs (3%). One month following above knee femoropopliteal bypass (48 limbs), patients with a popliteal-ankle difference less than 10 mmHg obtained a significantly higher ankle pressure index (PI 0.86, range 0.56-1.20) (p less than 0.01) than those with a pressure difference exceeding 10 mmHg (PI 0.66, range 0.40-0.91). The clinical state 6 months following femoropopliteal bypass did not demonstrate that patients with a low popliteal-ankle difference fared better than patients with a higher pressure difference; however, the PI appeared significantly lower in the latter group compared to the former. The graft material was correlated to the popliteal-ankle pressure difference. It appeared that prosthetic grafts failed within 6 months when the difference exceeded 10 mmHg in 10/12 limbs (83%), but autologous vein grafts only failed in 2/10 limbs (20%). Finally, it was possible to predict the postoperative ankle pressure index significantly from data derived from the pressure measurements.

Plasma angiotensin II concentration gradients across the pulmonary vascular bed were measured during diagnostic renal venous/right heart catheterization in twenty-seven hypertensive patients with renal or renovascular disease. There was a linear correlation between the plasma angiotensin II concentration in mixed venous blood and in systemic arterial blood. The pulmonary angiotensin II production rate was measured in fourteen patients. This parameter was linearly correlated with plasma renin concentration in systemic arterial blood. The plasma clearance of angiotensin II across the systemic vascular bed varied from 0.7 to 1.71/min, i.e. within a fairly narrow range.

The effect of ethanol (5--25 mM) on the galactose elimination kinetics in the intact liver was studied in the isolated perfused pig liver, using the steady-state infusion technique. Ethanol reduced galactose-Vmax on average to 0.07 mmol/min kg liver in six experiments from 0.43 mmol/min kg obtained in control experiments without ethanol. Also Km was significantly reduced from 0.23 mmol/l plasma water to 0.03 mmol/l. Ethanol increased UDP-galactose ten-fold simultaneous with a rise in hepatic outflow ratio of lactate to pyruvate to about 300 from 10; this indicates that ethanol inhibits epimerase. In experiments with increasing galactose elimination rates, the concentration of galactose-1-P increased much less than the concentration of galactose, and the phosphorylation of galactose therefore seems to be rate-limiting. In vitro galactokinase is inhibited by galactose-1-P. In the present study ethanol increased galactose-1-P five to ten times, and the reduction of Vmax and Km by ethanol could be explained by uncompetitive inhibition by galactose-1-P with Ki about 0.1 mmol/l. Ethanol decreased UDP-glucose to about 40% and UTP to less than 5%, probably due to trapping as UDP-galactose. This may depress the forward transferase reaction, and therefore the other co-substrate galactose-1-P rises--and inhibits galactokinase.

Forty-one reconstructive procedures were carried out in thirty-five consecutive patients. Average age was 63 years (range 46-75). Thrombendarterectomy or by-pass procedures were carried out in twenty-nine proximal and twelve femoropopliteal reconstructions. Twenty-three patients had rest pain fifteen had ischemic ulcers. The preoperative median pressure index (per cent of arm systolic pressure) was 10% on the 1st toe. At the 10th postoperative day the median toe pressure rose to 25%. A further rise took place at the one month control to 30% which was unchanged throughout the study. All patients with a persistent postoperative toe pressure above 20% of arm systolic pressure were ultimately relieved from rest pain and chronic ulcers.

A total of 107 patients suffering from intermittent claudication (CI) was studied after a mean observation time of 5.9 years. Thirty-one (29%) had died during the observation period. A questionnaire was sent to 76 patients and 78% replied. All patients were under 50 years of age at the first consultation. No patients had been operated upon. The ratio women:men was 1:1.3. 33% received disability pensions or some other kind of pensions. Fifty-eight had limited their spare-time activities because of CI. It is concluded that a close control and reconstructive arteria surgery must still be recommended when the working ability is threatened.

The peripheral run-off arteries were insufficiently visualized due to occlusions in the aorto-iliac segments in studies of 10 patients (15 legs) in 183 consecutive aorto-femoral angiograms. Guided by a combination of the Doppler technique and fluoroscopy, the non-opacified and pulseless common femoral artery was catheterized. Angiography through this catheter usually showed patency of a part of the common femoral artery but occlusion of the superficial femoral artery. The deep femoral and crural arteries were well preserved. Intra-arterial pressure measurements showed larger pressure gradients along the occluded aorto-iliac segments in one-third of the patients with non-visualized leg arteries as compared with gradients in patients with similar proximal and distal occlusions but with good opacification of the leg arteries. In previous cases, non-visualization of the leg arteries was considered as representing non-reconstructable lesions by our vascular surgeons. The findings in the present study showed that in these patients surgical reconstruction of only the aorto-iliac segments will suffice to save the limb from amputation.

19 patients with obstructive arterial disease both proximal and distal to the inguinal ligament were studied with segmental blood pressure recordings because reconstruction of the proximal lesion was considered. The common femoral pressure was measured intraarterially as well as with a 12 cm cuff placed as proximally as possible on the thigh. The proximal pressures measured by the two techniques were found to correlate well. Thus, the atraumatic cuff pressure technique is validated which can be of use in evaluating multilevel occlusions and the associated run off problem involved in partial proximal reconstruction.

Simultaneous measurement during 24 h of mean arterial blood pressure (MABP) and forefoot subcutaneous adipose tissue blood flow (SBF) was undertaken in eight patients (15 feet) with different degrees of arterial insufficiency. The recordings were undertaken with the patients in the supine position only. The MABP decreased by 19 +/- 9% from awake to asleep independently of symptomatology. In two limbs with normal circulation, SBF decreased by 8 +/- 7%. In five limbs with arterial insufficiency but no rest pain SBF decreased by 16 +/- 8%, and in eight limbs with ischaemic nocturnal rest pain, SBF was reduced by 32 +/- 12% during sleep. It is concluded that nocturnal hypotension is the major aethiological factor for the symptom ischaemic nocturnal rest pain.

To establish whether re-occlusion of the femoral artery could be prevented, in 6 consecutive patients undergoing percutaneous transluminal angioplasty (PTA) for superficial femoral artery occlusion the recanalised segment was isolated, with a 7-French double-balloon catheter. 5 mg recombined human tissue-type plasminogen activator (rt-PA) and 1000 IU heparin were then infused into the enclosed space for 30 minutes, followed by intravenous heparin for 24 hours. At 10 and 30 days all 6 patients had evidence of recanalisation and remission of symptoms. Mean ankle-arm pressure index improved by 72% at 24 hours, by 118% at 10 days, and by 103% at 30 days after the procedure. No patients had major complications. Treatment of superficial femoral artery occlusions by PTA with rt-PA and intravenous heparin seems to prevent rethrombosis.

The effects of acebutolol (with intrinsic sympathomimetic activity (ISA] and metoprolol (without ISA) on arm blood pressure, ankle systolic blood pressure, claudication distances (CD) and maximal walking distances (MWD) were compared in patients with essential hypertension and intermittent claudication. Fourteen patients participated in a long-term, open, randomized cross-over study. After randomization the patients received either acebutolol, 200 mg b.i.d., or metoprolol, 100 mg b.i.d. After eight weeks the drugs were shifted and after another eight weeks they were withdrawn. Arm and ankle blood pressure, CD and MWD were determined before randomization and after 4, 8, 12 and 16 weeks, and again 4-6 weeks after withdrawal of the drugs. The arm blood pressure was reduced by 20/13 mmHg after acebutolol and by 22/21 mmHg after metoprolol. In spite of a significant decrease in arm blood pressure there were no significant changes in ankle blood pressure, CD or MWD after the two drugs. After withdrawal of the drugs and after the arm blood pressure had returned to the control value no significant changes were seen in CD, MWD or ankle blood pressure. It is concluded that beta-blockers have no deleterious effect on CD, MWD or ankle blood pressure in patients with hypertension and intermittent claudication. No effect of ISA was demonstrated.

Forty-two patients, mean age 68 years, with severe leg ischaemia were randomly treated with placebo or by controlled defibrination with ancrod for 3 weeks. Plasma fibrinogen concentration was kept at about 20% of normal in the ancrod treated group. The two groups proved to be well matched regarding factors which could affect the degree of ischaemia. Objective measurements showed a significant rise in ankle and toe systolic blood pressure in the ancrod group lasting for 3 months. There was no rise in distal blood pressure in the control group. In the ancrod treated group the toe and ankle systolic pressures rose about 8 mmHg, but this was not accompanied by an improvement in the clinical course.

The fate of 257 consecutive patients (100 women) aged 36-85 years (mean 65) first seen with intermittent claudication in 1977 was analysed after a mean of 6.5 (SD 0.5) years. When first seen none of the patients complained of rest pain or had ulcers or gangrenous lesions on the feet. At follow up 113 of the patients (44%) had died. Causes of death were no different from those in the general population. Mortality was twice that of the general population matched for age and sex. Mortality among the men was twice that among the women. In men under 60 mortality was four times that expected. The rate of clinical progression of the arteriosclerotic disease (that is, rest pain or gangrene) of the worst affected leg was 7.5% in the first year after referral. Thereafter the rate was 2.2% a year. An ankle systolic blood pressure below 70 mm Hg, a toe systolic blood pressure below 40 mm Hg, or an ankle/arm pressure index below 50% were individually significantly associated with progression of the arteriosclerotic disease. These findings show the importance of peripheral blood pressure measurements in the management of patients with intermittent claudication due to arteriosclerotic disease.

101 gastrobioptic series from 93 consecutive patients with a final diagnosis of carcinoma of the stomach were reviewed. 20 false negative cases were found. Of these, ten cases were missed because of erroneous histopathological interpretation, two because of too few sections, and eight because carcinoma was not represented in the biopsies. The frequency of false negatives was slightly larger in ulcerating carcinomas than in polypoid and diffusely spreading carcinomas, mainly due to seven cases of ulcerating carcinoma being missed by the pathologist. There was no correlation between false negatives and histological type. The rate of false negatives was significantly higher in cases, where the number of biopsies taken was below seven. The rate of histopathological misinterpretations was significantly higher in cases, where the number of actually positive biopsies was below four. Attempts to increase the positive yield should be based on not only an evaluation of the biopsy technique, but also an analysis of the histopathological method and interpretation.

Regional 133Xe ventilation/perfusion studies were used to predict residual lung function after pulmonary resections. The accuracy of the method was good as checked by postoperative spirometry in 11 patients. In 25 patients with impaired lung function and pulmonary cancer, who were consecutively selected for surgery, the predicted postoperative maximal breathing capacities (MBC) ranged from 17 to 41 l/min-1 m-2. No patients became permanent pulmonary invalids. One patient died from myocardial infarction, 7 had transient pulmonary insufficiency and 17 patients survived operation without complications. Perfusion studies alone proved as reliable as perfusion/ventilation studies.

In experimental liver failure (pigs with totally devascularized liver) the effect of different types of extracorporeal hepatic assistance was evaluated. Group I (N = 6) were untreated controls, Group II (N = 6), simple cross-circulation, Group III (N = 6), cross-circulation with inflow in the donor directly into the portal vein and Group IV (N = 4), cross-perfusion with isolated perfused liver. The cross-circulation was started 20 h after devascularization. There was no change in survival time. Bilirubin was decreased by a factor of 2 and the prothrombin index increased by a factor of 2 after initiation of the cross-circulation due to the dilution. In contrast to this, ammonia was unchanged. During the perfusion no significant changes were found. In Group V (N = 4), extended cross-perfusion with isolated perfused liver for 20 h, starting just after exclusion of liver function in the recipient and with a new liver in the perfusion system every 6th hour, the survival time was significantly increased. Furthermore, changes in the biochemical variables were prevented. It is concluded that with a supply of quantitatively sufficient hepatic assistance it is possible to extend the survival time in experimental liver failure.

To evaluate the influence of necrotic liver tissue on the cerebral metabolism and cerebral function in acute liver failure, comparison was made between hepatectomy and total liver devascularization in pigs. In both groups the cerebral blood flow and glucose uptake were significantly decreased. The cerebral oxygen uptake was not reduced. The EEG frequency gradually fell from 12-14 Hz to 1-2 Hz, with intermittent and finally persistent flattening of cortical activity. The visual evoked potentials were unchanged throughout the observation period. The vascular autoregulation and the CO2-reactivity of cerebral circulation disappeared, indicating complete vasoparalysis. As no difference was found between the two groups, it is concluded that the encephalopathy was not due to intoxication from necrotic liver tissue in the abdominal cavity, but to deprivation of liver function.

We report the results of 50 angioplasty procedures via the popliteal artery. A 3-year follow-up including control of blood pressures at ankle and toe levels show results comparable to reports in the literature. This new approach for angioplasty of the superficial femoral artery and eventually of coexisting iliac lesions enables treatment of previously inaccessible lesions. The technique is especially suited for lesions close to the takeoff of the superficial femoral artery.

The effect of head-up tilt on leg blood flow and segmental arterial blood pressures was studied in 21 patients with occlusion or severe stenosis of the common or superficial femoral artery. Arterial pressure was measured directly in the brachial artery, common femoral artery and popliteal artery. Relative change in blood flow in the leg during tilt was estimated by changes in arterio-venous oxygen differences and by the indicator dilution technique in nine patients. Head-up tilt caused a decrease in leg blood flow of 36% corresponding to an increase in total vascular resistance of 57%. Tilt did not change the pressure gradient from femoral to popliteal artery in the patients with occlusion of the superficial femoral artery, indicating that the flow resistance offered by the collateral arteries had increased. In a bilateral sympathectomised patient the increase in collateral resistance was almost absent indicating that the constriction of the collateral arteries is mainly mediated via sympathetic vasoconstrictor fibres.