Skin perfusion patterns (fluorescein perfusography) during reactive hyperaemia in peripheral arterial occlusive disease.

From the pathophysiological point of view the regional distribution of blood flow is of special importance in ischaemic tissues. Within this study foot sole skin perfusion was investigated by means of fluorescein perfusography at rest and during reactive hyperaemia in patients with peripheral arterial occlusive disease confined to one limb (Fontaine stage II). Ambient temperatures were maintained around 21 degrees C. Mean fluorescein appearance times on the one side and their standard deviations (SD) and coefficients of variation (CV) on the other side were taken as measures of overall blood supply and homogeneity of flow, respectively. At rest no differences in these parameters could be detected between diseased legs and controls. After a 3-min supra-systolic circulatory arrest at the thigh, a significant reduction of fluorescein appearance times was observed for both groups but was statistically more pronounced in the controls. Furthermore, during reactive hyperaemia standard deviations as well as coefficients of variation decreased significantly only in normal limbs whereas they either remained constant (SD) or even increased (CV) in those with arterial obstructions. All effects associated with reactive hyperaemia showed statistically significant correlations with systolic ankle pressure indices. From these results it is concluded that haemodynamically effective arterial obstructions are followed by not only a restriction of overall hyperaemic blood supply but also a failure to homogenize microcirculatory perfusion in the case of increased flow requirements.     

Influence of peripheral arterial occlusive disease on muscular metabolism

Summary The concentrations of lactate, ammonia and hypoxanthine were determined in blood from the femoral artery, femoral vein and cubital vein under resting conditions in 23 patients with stage II, 10 patients and 20 diabetics with stage IV peripheral arterial occlusive disease (PAOD) and in 19 healthy subjects. The metabolite concentrations were also measured immediately and 20 min after calf exercise in the patients with stage II PAOD and in the controls. At rest, there was a negative arteriovenous difference in femoral lactate level and a positive arteriovenous difference in the ammonia level in all groups. After exercise to the claudication limit, the femoral venous concentration and arteriovenous difference for lactate increased in the patient group significantly higher than in the controls, who were exercised three times as heavily. Furthermore, there was a significant rise in femoral venous ammonia concentration with inversion of the arteriovenous difference into the negative range and an increase in femoral venous hypoxanthine concentration only in the patients with PAOD and not in the controls. A significant correlation was found between the exercise-induced increases in lactate and ammonia. The results indicate activation of the purine nucleotide cycle in the muscles of limbs with impaired circulation, even for a short duration of load. This can be explained by activation of the AMP-deaminase in type I and type IIa muscle fibres by anoxaemia. The purine nucleotide cycle has an emergency metabolic function in ischaemia to maintain muscle contractility. Ammonia determination in femoral blood permits, in association with lactate and hypoxanthine determination, a precise quantitative assessment of the metabolic effects of PAOD.Abbreviations ADP adenosine diphosphate - AMP adenosine monophosphate - ATP adenosine triphosphate - AVD arteriovenous difference - IMP inosine monophosphate - PAOD peripheral arterial occlusive disease - PNC purine nucleotide cycle Dedicated to Prof. Dr. R. Hild on the occasion of his 60th birthday     

Influence of peripheral arterial occlusive disease on muscular metabolism

Summary The metabolites pyruvate, alanine and urea were determined under resting conditions in blood from the femoral artery, femoral vein and cubital vein of 23 patients with stage II, 10 patients and 20 diabetics with stage IV PAOD as well as 19 healthy volunteers. Measurements were also carried out immediately and 20 min after ergometric calf exercise in the patients with stage II PAOD and the controls. In both patient groups with stage IV PAOD, there were lower arterial and venous alanine levels and higher urea concentrations at rest than in patients with adequate resting circulation, which is evidence for increased hepatic alanine extraction. After exercise, a significantly higher increase in the arteriovenous difference of pyruvate concentration was to be found in the patient group with stage II PAOD than in the control group. Moreover, there was a significant increase in femoral venous concentration and a rise in the arteriovenous difference of alanine, indicating muscular release, only in the PAOD patients and not in the volunteers in spite of a three times higher exercise load. The exercise-induced rise in femoral venous alanine correlated closely with those of pyruvate and ammonia. Alanine formation fulfills the function of a non-toxic carrier of muscularly produced amino groups and represents in PAOD a compensating mechanism that delays the limitation of muscular contractility. Alanine determination, especially in association with an exercise test, appears to be suitable for assessing the extent of anaerobic energy production in muscles of limbs affected by PAOD.Abbreviations AMP adenosine monophosphate - ATP adenosine triphosphate - AVD arteriovenous difference - GPT glutamate pyruvate transaminase - LDH lactate dehydrogenase - NAD nicotinamide-adenine-dinucleotide - PAOD peripheral arterial occlusive disease - PNC purine nucleotide cycle Dedicated to Prof. Dr. R. Hild on the occasion of his 60th birthday     

Estimation of digital circulation and its correlation to clinical signs of ischaemia--a comparative methodological study

Five different methods were used to evaluate the arterial blood supply to 29 toes from 15 patients with atherosclerotic disease: digital pulse plethysmography, systolic toe blood pressure recording, skin temperature recording, vital capillary microscopy and dynamic fluorescein angiography. An optimal discrimination between legs with and without ischaemic ulcers or gangrene was obtained with the following borderlines: inclination time non-measurable because of very low or no recordable pulse curve, systolic toe blood pressure less than 20 mmHg, skin temperature (after vasodilatation) less than 29 degrees C, capillary stage greater than 3 (indicating the presence of capillary haemorrhages or more advanced changes) and fluorescein appearance time greater than 45 s. The results of the study provide no basis for the opinion that one method is superior to the others in discriminating between arteriosclerotic feet with and without existing skin necrosis.     

Increased serum laminin and angiogenin concentrations in patients with peripheral arterial occlusive disease.

AIM: To measure serum laminin and angiogenin concentrations in patients with peripheral arterial occlusive disease (PAOD) Fontaine stages IIb, III, and IV. METHODS: The study population comprised 38 patients (20 men and 18 women) with stage IV PAOD, 11 patients (six men and five women) with stage III PAOD, 18 patients (10 men and eight women) with stage IIb PAOD, and 23 patients (10 men and 13 women) with deep vein thrombosis. Fifteen normal subjects (matched for risk factors) and 10 patients (five men and five women) without PAOD served as controls. Serum samples were obtained at admission and serum laminin and angiogenin concentrations were measured using an enzyme linked immunosorbent assay. RESULTS: Patients with stage IV PAOD had higher serum laminin (mean +/- SEM; 826 +/- 97 ng/ml) and angiogenin concentrations (467 +/- 26 pg/ml) than normal subjects (laminin: 379 +/- 21 ng/ml; angiogenin: 358 +/- 16 pg/ml) and patients without PAOD (laminin: 277 +/- 34 ng/ml; angiogenin: 406 +/- 25 pg/ml). A significant correlation was found between angiogenin and laminin and between serum laminin and fibrinogen concentrations in patients with stage IV disease. CONCLUSIONS: Raised laminin and angiogenin concentrations may be indicators of endothelial damage caused by reduced vascular perfusion or compensatory revascularisation, or both.     

Sympathetic neuronal activity in diabetic and non-diabetic subjects with peripheral arterial occlusive disease

Summary Despite the vasoconstrictory influence of the-adrenergic system on the peripheral blood circulation the results of the sympathectomy were not satisfying in the therapy of peripheral arterial occlusive disease (PAOD). The aim of the present investigation was to clarify the pathophysiologic mechanisms of this clinical observation. Free and sulfoconjugated catecholamines were determined in the femoral artery, vein, and cubital vein of 19 healthy controls, 21 non-diabetic patients with PAOD stage II, 8 non-diabetic (PAOD IV) and 20 diabetic patients (D IV) with PAOD stage IV. In comparison with controls and group PAOD II an increased sympathoneuronal tone in group PAOD IV was evident at rest. Sympathetic activation was not restricted to the affected limb, since femoral and cubital venous norepinephrine levels were not different and plasma epinephrine fractional extraction (PEFE) was not altered by angiopathy. The lower sympathoneuronal activation in the group D IV may be attributed to an impaired pain perception or a reduced dopamine-hydroxylase activity indicated by a lower ratio of norepinephrine to dopamine. The failing long-term efficacy of lumbar sympathectomy in critical arterial limb disease may be explained by marked spontaneous sympathicolysis in diabetics, whereas in nondiabetics with sympathetic activation other mechanisms like development of unilateral Mönckeberg sclerosis, progression of proximal arterial occlusion or induction of steal effects have to be discussed.Abbreviations DA dopamine - DBH dopamine beta-hydroxylase - EGTA ethylene glycol-bis(-aminoethylether)-N,N,N,N-tetraacetic acid - EPI epinephrine - HPLCA high performance liquid chromatography with amperometric detection - NE norepinephrine - PAOD peripheral arterial occlusive disease - PEFE plasma epinephrine fractional extraction     

Relationships between skin temperature and perfusion in the arm and leg

Relationships between skin temperature (Tsk) and perfusion have been studied to provide a basis for the use of Tsk in the non-invasive assessment of limb circulation in peripheral vascular disease. Raising the ambient temperature (Ta) from 20 to 30 degrees C increased the perfusion of the glabrous skin of the hands and feet without changing that of the skin of the forearm or calf. On a fractional basis the response in the hand and foot was the same. Tsk was higher in the arms than the legs and in the proximal than distal parts of the limbs. A fall in Tsk was often seen when Ta rose from 20 to 25 degrees C and was attributed to counter-current cooling. Subsequently Tsk rose even in regions where there was no increase in skin perfusion. Tsk can only be related to its perfusion in the fingers, palm and toes. Forearm Tsk was related to the perfusion of the digits. This relationship implies a link with the arterial inflow to the limb which determines the size of its thermal core. Heat conduction from the core seemed important for the skin of areas like the forearm and calf where the constant, low perfusion limited the amount of heat which could be transported to it directly by the blood. The importance of conduction was supported by studies, at Ta 20 degrees C, on subjects during calf muscle exercise and on patients with arterio-venous fistulae. Here an increase in the arterial inflow to the limb was associated with a rise in Tsk of the forearm/calf unrelated to the perfusion of its skin.     

Extracorporeal blood oxygenation and ozonation (EBOO): a controlled trial in patients with peripheral artery disease

BACKGROUND: Since 1990 our group has been using extracorporeal circulation to ozonate blood by an original method, known as extracorporeal blood oxygenation and ozonation (EBOO), with the aim of amplifying the results observed with ozone autohemotherapy. OBJECTIVE: To verify the hypothesis that EBOO improves the skin lesions typical of peripheral artery disease (PAD) patients. METHODS: Twenty-eight patients with PAD were randomized to receive EBOO or intravenous prostacyclin in a controlled clinical trial. The primary efficacy parameters were regression of skin lesions and pain,and improvement in quality of life and vascularisation. RESULTS: Patients treated with EBOO showed highly significant regression of skin lesions with respect to patients treated with prostacyclin. Other parameters that were significantly different in the two groups of patients were pain,pruritus, heavy legs and well-being. No significant differences in vascularisation of the lower limbs before and after treatment were found in either group.No side effects or complications were recorded during the 210 EBOO treatments. CONCLUSION: EBOO was much more effective than prostacyclin for treating skin lesions in PAD patients and also had a positive effect on patient general condition without any apparent change in arterial circulation. This suggests other mechanisms of action of EBOO.     

Novel registration-based framework for CT angiography in lower legs

Proper subtraction and visualization of contrast-enhanced blood vessels in lower extremities using computed tomography angiography (CTA) is based on precise masking of all non-contrasted structures in the area, and it is the main prerequisite for correct diagnosis and decision on treatment for peripheral arterial occlusive disease (PAOD). Because of possible motion of patients during the CTA examination, precise elimination of non-contrasted tissues, including bones, calcifications, and soft tissue, is still very challenging for lower legs, that is, from knees to toes. We propose novel registration-based framework for detection and correction of the motion in lower legs, which typically occurs between and during CTA pre-contrast and post-contrast acquisitions. Within the framework, two registration cores are proposed as alternatives, and resulting CTA subtraction images are compared with Advanced Vessel Analysis considered one of the reference commercial tools among clinical applications for CTA of lower extremities. The CTA subtraction images of 55 patients examined for PAOD are evaluated visually by four expert observers on the Philips Extended Brilliance Workspace using four criteria assessing the overall robustness of tested methods. According to the complex evaluation, the proposed framework enabled valuable improvements of CTA examination of lower legs.     

Clinical study of therapeutic angiogenesis by autologous peripheral blood stem cell (PBSC) transplantation in 92 patients with critically ischemic limbs

Patients with critically ischemic limbs due to maintenance hemodialysis and diabetes are increasing in number markedly in Japan. The difficulty of treating critically ischemic limbs is well recognized. Despite active medication and surgical therapy, many critically ischemic limbs are amputated. Ninety-two patients with critically ischemic limbs were treated by transplantation of autologous peripheral blood stem cells (PBSCs). The stem cells were mobilized into the peripheral blood by administration of granulocyte colony stimulating factor (G-CSF). The mobilized mononuclear cells were separated by an apheresis technique using a centrifuge. The separated mononuclear cells contained approximately 4.0 × 10⁷ CD34-positive cells. The collected cell suspension was divided into aliquots of 0.5–1.0 ml and transplanted into the muscle of ischemic limbs at 50–70 transplantation points. At 1.5 months after PBSC transplantation, a strong immunostaining of CD34-positive cells and factor VIII, as well as capillary formation, was observed in the muscles into which stems cells had been transplanted. In each patient tested, the serum vascular endothelial growth factor (VEGF) level increased after stem cell transplantation; the mean VEGF level increased by 176%. Of 11 diabetic patients (DM) who were not receiving hemodialysis (HD), there were no amputees regardless of their Fontaine classification. Of 19 patients in the HD(+)DM(−) category, there were no amputations in Fontaine stage I, II, and III patients, whereas three limbs and one toe were amputated in Fontaine stage IV patients. Of 13 patients in the HD(−)DM(+) category, none of the Fontaine stage I, II, or III patients underwent amputation, but six Fontaine stage IV patients underwent amputation. Of 49 patients in the HD(+)DM(+) category, 38 (78%) were classified as Fontaine stage IV, 71% (27/38) of whom had a toe or a limb amputated. In nine patients over 80 years of age, one toe and one limb were amputated. Nondiabetic, nondialyzed patients with ischemic limbs are strongly indicated for stem cell transplantation regardless of Fontaine classification. Therapeutic angiogenesis is effective for critically ischemic limbs resulting from hemodialysis and diabetes until Fontaine stage III, but is of limited effectiveness for stage IV cases.     

Fusarium solani major allergen peptide IV-1 binds IgE but does not release histamine

BACKGROUND: Fusarium solani (FS) is an important allergen source afflicting 4% of the nasobronchial allergy patients. Fus s I3596*, a 65 kDa major glycoprotein allergen of FS reacts with 95% fungus sensitive patients. OBJECTIVES: To purify and characterize a potent peptide from Fus s I3596* which may be useful for therapeutic purposes. METHODS: The 65 kDa protein was sequentially cleaved with trypsin and cyanogen bromide (CNBr). The cleaved products were purified on reverse phase high performance liquid chromatography (rpHPLC) column and functionally characterized by in vitro and in vivo methods for its IgE binding and histamine release. RESULTS: The protein on cleavage showed 11 peaks (I to XI). Of these, peaks I, III, IV and V were highly allergenic as determined by IgE ELISA. These peaks were further purified and peptide IV-1 was most potent in comparison to other peptides by ELISA-inhibition. This peptide showed IgE binding but could not evoke intradermal response in Fusarium-sensitive patients. Heparinized blood challenged with peptide IV-1 does not release histamine. Preincubation of heparinized blood with peptide IV-1 and challenging with crude extract blocked histamine release in a dose dependent manner. CONCLUSION: Peptide IV-1 binds to IgE but does not release histamine, demonstrating its potential use in therapy of Fusarium-allergic patients.     

The effect of selected health, demographic and psychosocial aspects on quality of life in patients with peripheral arterial occlusive disease--a prospective analysis

BACKGROUND: Peripheral arterial occlusive disease (PAOD) is a prevalent atherosclerotic disorder characterized by exertional limb pain, loss of limb, and a high mortality rate. Because of its chronic nature, it often has a negative impact on a patient quality of life (QoL). Aims. To evaluate the effect of selected health, demographic and psychosocial aspects on QoL in respondents with PAOD. PATIENTS AND METHODS: The study is a prospective and cross-sectional. It was carried out at the 2nd Department of Medicine of Charles University Hospital at the Faculty of Medicine in Hradec Králové, Czech Republic. Forty two respondents with PAOD (28 male, 14 female) were evaluated. All the respondents had involvement of femoral and popliteal arterial circulation. The number of all respondents in accordance with Fontaine classification was as follows: intermittent claudication: stage IIa - 4, stage IIb (<200 m) - 16, stage IIb (<50 m) - 9, chronic limb ischaemia: stage III - 6, stage IV - 7. The average age of all respondents was 65,4 years old (age range 45-79 years old). The study evaluates the effect of health aspects (stage of PAOD in accordance with Fontaine classification, diabetes mellitus, arterial hypertension, hyperlipidaemia, obesity, smoking), demographic (age, sex) and psychosocial aspects (level of education, marital status, religion) on QoL in respondents with PAOD. The Czech version of the International Generic European Quality of Life Questionnaire - EQ-5D was used. RESULTS: The statistical evaluation presents statistically a significant dependence of QoL in respondents with PAOD on age (p < 0,01) and the stage of PAOD in accordance with the Fontaine classification (p < 0,01). The effect of other health, demographic and psychosocial aspects was statistically insignificant. CONCLUSION: The results had shown that with an increasing age and with a serious stage of PAOD in accordance with Fontaine classification, the QoL declines. The global QoL in respondents with PAOD is low.     

Hemodilution (HD) in patients with ischemic skin ulcers

Summary In 25 patients with arterial occlusive disease in the clinical stage IV according to Fontaine a hemodilution down to an average hematocrit value of 0.31±0.02 was performed. Eighteen patients had peripheral ulcers of the lower limbs and 3 patients had ulcers of the upper ones. Four patients had tissular lesions both at the level of the feet and toes and hand and fingers. The average age of the patients was 43. Hemodilution was achieved by repeated withdrawals of approx. 500 ml blood, followed by reinfusion of the autologous plasma associated with infusion of substitutive solutions of low-molecular weight dextran to avoid hypovolemia. In all patients with peripheral ulcers of the upper limbs, with no exception, a good to a very good clinical effect was obtained ranging from an extended to complete healing. The healing tendency of lesions in the feet and toe region was on the whole less marked and depended basically on the total number of vascular impediments found in one patient. The rheological and hemodynamic mechanism of the therapeutic effect of hemodilution, the preliminary criteria for indicating this therapy and its observed complications are discussed.Supported by Verein zur Bekämpfung der Gefäßerkrankungen e.V. Engelskirchen, Federal Republic of Germany     

Progression of diabetic retinopathy correlated with muscle perfusion disturbances of the lower limbs,with clinically important diagnostic recommendations

Introduction

The objective of this study was to investigate the relationship between microvascular and macrovascular disturbances in patients with type 2 diabetes, as shown by results of ophthalmological examination and by vascular and perfusion examinations of the lower limbs.

Material and methods

A total of 85 patients with type 2 diabetes and an additional cardiovascular risk factor were enrolled in the study. All patients underwent complex ophthalmological examination, including fundus colour photography and fluorescein angiography, and were divided into two groups: group I with signs of diabetic non-proliferative retinopathy (NPDR), and group II with signs of diabetic proliferative retinopathy (P/PDR). After collection of the general medical history and analysis of medical data, patients underwent vascular and muscle perfusion examination of the lower limbs.

Results

In the P/PDR group, disturbances of lower-limb perfusion were more frequent than in the NPDR group. Analysis of the blood flow and results of lower-limb muscle perfusion for the two groups showed a significant relationship with the severity of microvascular complications observed in examination of the fundus.

Conclusions

Ophthalmological assessment of the progression of diabetic retinopathy in patients with type 2 diabetes is a reliable indicator of the changes in peripheral vessel systems and perfusion defects in the lower limbs.     

Fourier analysis of impedance rheography for peripheral arterial occlusive disease

This study identified those harmonics from the frequency spectrum of electrical impedance rheographic signals that discriminate between patients with and without peripheral arterial occlusive disease (PAOD). Ninety-four patients with suspected PAOD were evaluated by impedance rheography and ankle-arm blood pressure index. The leg with the lower ankle-arm index was used in the analysis and a haemodynamically relevant PAOD was assumed at an ankle-arm index lower than 0.85. The frequency spectrum of the impedance signals of the shank was calculated by means of a fast Fourier transformation algorithm. The first ten harmonics were used as independent variables in a stepwise logistic regression analysis to evaluate the dependent variable PAOD. In the regression analysis only the third harmonic was accepted (P<0.0001). The correct classification of the patients was 90%. In conclusion, by means of Fourier analysis of impedance rheographic signals, a high accuracy in the diagnosis of PAOD can be achieved. Electronic Publication     

Disturbances in pulmonary gaseous exchange in primary hyperlipoproteinemias.

Carbon monoxide diffusion (DLCO), blood gas analysis at rest and after exercise, distribution of ventilation and perfusion by Xenon 133 were carried out in 43 hyperlipidemic patients, Fredrickson's types I, IIA, IIB, and IV. DLCO was significantly reduced in hypertriglyceridemic and to a lesser degree in hypercholesterolemic patients. A significant negative correlation was found between DLCO and triglyceride values. Significantly lower basal PaO2 values, which improved after exercise, were observed in both type IIA and type IV hyperlipemic patients. The ventilation/perfusion ratio distribution (V/Q) did not increase from the basal to the apical segments of the lungs in hyperlipidemic patients as it did in normals. The hypothesis of an alteration in pulmonary surface-active lipoprotein, directly related to hyperlipoproteinemia or indirectly caused by fat microembolism, may explain the reduced DLCO, the loss of V/Q gradient, and the decrease in PaO2 (which improves after exercise) observed in hyperlipemic patients. Disturbances in pulmonary gas exchange and PaO2 reduction could play an important role in the pathogenesis of both angina pain due to ischaemic heart disease, which is frequently observed in hyperlipemic patients, and the postprandial angina syndrome.     

Skin perfusion pressure measured by isotope washout in legs with arterial occlusive disease. Evaluation of different tracers, comparison to segmental systolic pressure, angiography and transcutaneous oxygen tension and variations during changes in systemic blood pressure

The skin perfusion pressure (SPP) measured as the isotope washout cessation external pressure is valuable in selection of major amputation level. Five methodological investigations important to clinical use were carried out: (1) In five normal legs and 10 legs with arterial occlusive disease (AOD), 131I- -antipyrine (131I- -a.p.) was compared to Na(131I-) and 99Tcm-pertechnetate (99Tcm). The average SPP by 131I- -a.p. and by 131I- were approximately equal, 57.0 mmHg (range 18-93) compared to 56.3 mmHg (range 13-88) (P greater than 0.1). The average SPP by 99Tcm was just slightly higher, 60.3 mmHg (range 18-98) (P less than 0.02). The average washout constant for the three different tracers were approximately equal and correlated statistically significant with the SPP; (2) In 59 legs with AOD, segmental SPP was compared to segmental systolic blood pressures on the thigh, calf, ankle and first digit (strain gauge technique). The two different methods correlated statistically significant at all four levels, but the systolic blood pressures were higher than the SPP in particular in diabetic legs; (3) Angiograms in 35 legs with AOD showed that the SPP on the ankle was only consistently decreased in legs with arterial occlusions at two levels or more; (4) In 47 legs with AOD, the SPP on the calf or on the thigh was compared with transcutaneously measured pO2. The two different methods correlated statistically significant, but the scatter was great; (5) During induced variations in systemic blood pressure in seven patients (12 legs with AOD), the segmental SPP and the segmental systolic blood pressure were found on average to vary in proportion with intra-arterial mean and systolic pressure respectively; however, this proportional relationship was not valid for the individual leg. It is concluded that 99Tcm is as suitable as the 131I- -labelled tracers in estimating the SPP. The SPP is significantly correlated to skin blood flow, to systolic blood pressure, to tc pO2 and to angiographic findings. Correction of SPP for systemic blood pressure changes can be made in proportion with the measured variations in systemic mean blood pressure, but only for groups of patients.     

Local regulation of subcutaneous blood flow and capillary filtration in limbs with occlusive arterial disease. Studies before and after arterial reconstruction

The aim of the study was to examine the local blood flow regulation and the capillary filtration rate in patients with occlusive arterial disease before and after arterial reconstructive surgery. Fourty-seven normal subjects and 99 patients were studied. Subcutaneous blood flow was measured on the forefoot by the local 133Xenon method. Forefoot arterial blood pressure was measured indirectly by cuff and strain-gauge technique. Capillary filtration rate was measured by strain-gauge plethysmography on the forefoot. The arterial and venous pressures of the forefoot were changed by elevating or lowering the foot in relation to heart level. In normal limbs autoregulation was demonstrated during elevation of the limb when blood flow remained almost constant despite the reduction in arterial and perfusion pressures. The local vasoconstrictor response to increased venous transmural pressure was demonstrated when the limb was lowered and blood flow decreased about 30% despite a constant perfusion pressure. In limbs with occlusive arterial disease both local blood flow regulation mechanisms became progressively more abnormal the severe the symptoms and the lower the distal blood pressure. Estimations of the changes in local vascular resistance suggested that the abnormalities in blood flow regulation in all but the severest cases are the result of changes in local perfusion pressure rather than the result of inability of the arteriolar smooth muscle to dilate and constrict in response to changes in arterial and venous pressures. After arterial reconstruction the two mechanisms generally normalized within about a week. However, disturbances occurred in some cases in the early postoperative period, possibly as the result of postoperative pain and stress. Postreconstructive hyperaemia developed in most limbs despite the early normalization of local blood flow regulation. Compared with normal limbs, the forefoot capillary filtration rate was reduced in limbs with occlusive arterial disease. In the early postoperative period the filtration rate remained reduced, but it increased to normal values within three months. Postreconstructive oedema developed independently of the normalization of blood flow regulation, and almost exclusively after femoro-distal by-pass surgery. The study supports the hypothesis that the postreconstructive oedema is a lymphoedema due to surgical trauma, rather than the result of microvascular derangement.     

External work is deficient in both limbs of patients with unilateral PAD

External work was utilized to measure differences between the unaffected and the affected limb in patients with unilateral peripheral arterial disease compared to healthy controls. Patients with unilateral peripheral arterial disease have shown deficits in peak joint powers during walking in the unaffected and affected legs. However, no research has detailed the amount of work that is being performed by each leg compared to healthy controls even though such an analysis would provide valuable information on the energy output from the affected and the unaffected legs. Two hypotheses were tested: (a) the unaffected and affected leg would perform less work than healthy controls in a pain-free state, and (b) the onset of symptomatic claudication pain would result in further changes in the external work. Results showed that during a pain-free state, both the unaffected and affected legs perform less work than the healthy controls. After onset of claudication pain, the work output by the affected limb becomes further decreased while the unaffected limb experiences changes in negative external work. These findings combined with recent evidence of decreased peak powers in both legs in unilateral peripheral arterial disease patients reflects altered pathomechanics in both limbs compared to healthy controls.     

Latent and lytic HHV-8 mRNA expression in PBMCs and Kaposi's sarcoma skin biopsies of AIDS Kaposi's sarcoma patients

Human herpes virus 8 (HHV-8) is associated with all clinical forms of Kaposi's sarcoma. HHV-8 DNA is present in Kaposi's sarcoma biopsies and is observed regularly in saliva and less consistently in blood of Kaposi's sarcoma patients. The expression pattern of latent (ORF 73) and lytic (vGCR, vBcl-2, and vIL-6) HHV-8 mRNA was studied in peripheral blood mononuclear cell (PBMC) samples and Kaposi's sarcoma skin biopsies from 11 AIDS Kaposi's sarcoma patients with four different nucleic acid sequence-based amplification (NASBA) assays. Patients were divided into groups according to the clinical stage of Kaposi's sarcoma (stage I-IV). All biopsies were positive for two or more of the mRNA measured. No clear difference could be seen in the expression pattern in the lesions of the different clinical stages. In the corresponding PBMC samples, very little or no mRNA was measurable in the patients with Kaposi's sarcoma stage I or II, whereas patients with more advanced Kaposi's sarcoma (stage III or IV) had more detectable mRNA in the PBMCs. Thus, the HHV-8 DNA load in the PBMCs increases in more advanced Kaposi's sarcoma, as does the frequency of mRNA detection in PBMCs.