The challenging topic of diabetic foot revascularization: does the angiosome-guided angioplasty may improve outcome.

The angiosome model was first pioneered by Jan Taylor in 1987 by his influential anatomical works in the plastic reconstructive surgery field. The concept depicts the human body into three-dimensional blocks of tissue, fed by specific arterial and venous irrigation sources, the "angiosomes". Adjacent angiosomes are linked by a vast compensatory collateral web "the choke vessels". This collateral network provides a remarkable "rescue system" in non-atherosclerotic and non-diabetic patients. However, it could be dramatically damaged in chronic limb ischemia (CLI) subjects witnessing miscellaneous systemic arterial disease. The angiosome concept may provide useful information on the human vascular anatomy and related pathology, with specific applications in surgical and vascular interventional therapies. This knowledge may become particularly beneficial in CLI while treating advanced atherosclerotic disease that adds extended collateral depletion. The concept may allow to deliberately focus arterial flow reconstruction in specific limb ischemic areas that exhibit tissue loss and fluctuating "rescue-vessels" supply. The implementation of angiosome-derived strategies in Rutherford grade III CLI presentations, may afford encouraging wound healing and limb preservation rates for both, bypass or endovascular techniques. The present paper proposes a parallel review of the main contemporary publications that share this theory in dedicated CLI literature, with practical considerations for its daily use. Recent applications of the angiosome concept in current CLI revascularization seem to evince benefic results in tissue cicatrization, although comparative and prospective data are further mandatory to cast any pertinent clinical validation.

Tibial microdissection for diabetic wounds.

Few data are available focusing on controlled blunt microdissection during below-the-knee interventions as sole or synchronous technique coupled to subintimal angioplasty, particularly in the management of diabetic critical-ischemic foot wounds. We present two cases of targeted recanalizations in the tibial and pedal trunks for plantar and forefoot diabetic ischemic tissue defects, following an angiosome-model for perfusion.

Combined primary subintimal and endoluminal angioplasty for ischaemic inferior-limb ulcers in diabetic patients: 5-year practice in a multidisciplinary 'diabetic-foot' service.

INTRODUCTION: This study aims to assess the patency, the clinical success and the limb-salvage rates of combined subintimal (SA) coupled to endoluminal angioplasty (EA) as the initial treatment of ischaemic inferior-limb ulcers in diabetic patients and to study the influence of other concurrent factors in the tissue-healing process. MATERIALS AND METHOD: Since September 2002 until December 2007, a consecutive series of 176 limbs with manifold ischaemic wounds in 161 diabetic patients were treated by associated multilevel angioplasties in a multidisciplinary 'diabetic-foot team' (a third-line diabetic-care institution integrating two departmental hospitals). There were 98 associated SA with EA procedures, 26 re-vascularisations by single SA technique and 52 others including selective multilevel EAs that were retrospectively reviewed. The mean follow-up period was 22.1 months (in the range of 1-50 months) by clinical and duplex evaluation (every 6 months). RESULTS: The initial technical success was noted in 149 limbs (84%). For the single or associated SA procedures, 102 of 124 procedures were successful (82%) and 145 of 150 of the miscellaneous EAs (96%) evinced an equally favourable outcome. The 27 initially failed endovascular procedures (22 SA and five EA) required 16 surgical re-vascularisation, eight adjuvant endovascular procedures besides three amputations. A total of 21 secondary and five tertiary angioplasties were equally necessary during the entire follow-up period of these patients. The 30-day survival rate was 99% (one patient died from myocardial infarction). In a intention-to-treat analysis, the cumulative primary and secondary patencies at 12, 24, 36 and 48 months were 62%, 45%, 41% and 38%, together with 80%, 69%, 66% and 66%, respectively. The aggregate clinical success rates at the same intervals were 86%, 77%, 70% and 69%, while the corresponding limb-salvage proportions showed 89%, 83%, 80% and 80%, respectively. The primary patency was negatively affected at 1 and 4 years by the length of the occluded segment (>10 cm) and the end-stage renal disease (ESRD) (p<0.0001). The limb-salvage rates were unfavourably influenced at the same periods by the extent of tissue defects (>3 cm), the ESRD and the presence of osteomyelitis. In addition, at 4 years, the age (>70 years), the accompanying peripheral neuropathy, the bedridden status and the presence of cardiac failure (left ventricular ejection fraction (LVEF)<30%) appeared equally as negative predictors (p<0.0001) for wound healing and limb rescue. CONCLUSION: Primary angioplasty represents a low aggressive and efficacious method to improve the healing process in diabetic ischaemic ulcers. However, beyond appropriate re-vascularisation, even repetitive if necessary, achieving satisfactory limb-salvage rates probably implies a multidisciplinary control of the presenting risk factors for wound healing as well.

Assessment of determinants for osteoporosis in elderly men.

SUMMARY: The aim of this cross-sectional study was to determine and quantify some determinants associated to low bone mineral density (BMD) in elderly men. This study showed that ageing, a lower body mass index (BMI), a higher blood level of C-terminal cross-linking telopeptides of type I collagen (CTX-1), family history of osteoporosis, and/or fracture and prior fracture were associated with bone mineral density. INTRODUCTION: Our aims were to identify some determinants associated to low bone mineral density in men and to develop a simple algorithm to predict osteoporosis. METHODS: A sample of 1,004 men aged 60 years and older was recruited. Biometrical, serological, clinical, and lifestyle determinants were collected. Univariate, multivariate, and logistic regression analyses were performed. Receiver operating characteristic analysis was used to assess the discriminant performance of the algorithm. RESULTS: In the multiple regression analysis, only age, BMI, CTX-1, and family history of osteoporosis and/or fracture were able to predict the femoral neck T-score. When running the procedure with the total hip T-score, prior fracture also appeared to be significant. With the lumbar spine T-score, only age, BMI, and CTX-1 were retained. The best algorithm was based on age, BMI, family history, and CTX-1. A cut-off point of 0.25 yielded a sensibility of 78%, a specificity of 59% with an area under the curve of 0.73 in the development and validation cohorts. CONCLUSION: Ageing, a lower BMI, higher CTX-1, family history, and prior fracture were associated with T-score. Our algorithm is a simple approach to identify men at risk for osteoporosis.

Why a multidisciplinary team may represent a key factor for lowering the inferior limb loss rate in diabetic neuro-ischaemic wounds: application in a departmental institution.

UNLABELLED: INTRODUCTION/AIM OF THE STUDY: To assess the influence of a multidisciplinary approach on the limb salvage rates in the treatment of patients suffering from diabetic ischaemic inferior limb ulcers. MATERIALS & METHOD: From September 2001 until March 2008, a consecutive series of 183 limbs with diabetic ischaemic wounds in 163 patients were treated by combined multi-level angioplasties as the primary revascularization approach in an institutional diabetic programme (two departmental hospitals). The avoidance of limb loss was retrospectively analyzed before and after the year 2005, as a landmark for implementing a "multidisciplinary diabetic foot clinic" in the routine daily care. RESULTS: Initial technical success for endovascular revascularization was noted in 152 limbs (83%). The aggregate limb salvage proportions at 12, 24, 32, 60 and 66 months (+/- SEM) were: 87% (+/- 2.8), 80% (+/- 3.9), 77% (+/- 4.4) and thereafter 77% (+/- 4.4), respectively. A comparison between the limb salvage rates before and after initiating the multidisciplinary group showed a significant difference (p = 0.040, CI: 1.040-5.311, HR: 2.35, Chi square = 4.22) with better results in the latest interval, employing effective team activity. No statistical deviation was found regarding the technique itself for revascularization at the same intervals (p = 0.381). CONCLUSION: Our experience suggests that limb salvage for diabetic ischaemic wounds may be favourably influenced by a co-ordinated multidisciplinary group. Although appropriate revascularization is crucial for limb rescue, a pluralist control of the attending risk factors influencing wound healing might be of matchless importance as well.

Investigations of factors influencing exposure and response to lead, mercury, and cadmium in man and in animals.

The susceptibility of the heme biosynthetic pathway to lead, as reflected by increased free erythrocyte porphyrin (FEP) concentration, is in humans as well as in rats in the order of young greater than or equal to female greater than male. The difference between adult male and female rats can be explained at least partially by the interaction of estradiol and progesterone with the FEP response to lead; the hormonal influence on FEP does not seem to be mediated through changes in plasma iron. The classical "tubular type" proteinuria in workers chronically exposed to cadmium has two not necessarily concomitant components, namely, a tubular type and a glomerular type component characterized by increased excretion of low and high molecular weight proteins, respectivley. No synergistic effect of cadmium and lead on the proteinuria of workers simultaneously exposed to both metals was observed. Mercury (most likely methylmercury) is freely transferred from the mother to the fetus; there is only a slight placental barrier for lead and a rather strong one for cadmium. Compared to maternal blood, placenta does not accumulate lead or mercury but concentrates cadmium about 10-fold.

Placental transfer of lead, mercury, cadmium, and carbon monoxide in women. II. influence of some epidemiological factors on the frequency distributions of the biological indices in maternal and umbilical cord blood.

PIP: Various epidemiological factors (smoking, residence, age, occupation, drinking habits, duration of pregnancy, and number of previous pregnancies) were investigated in 474 pregnant women (European) and their newborns to assess the effects of these factors on the presence of lead, mercury, cadmium, and carbon monoxide in blood of mothers and newborns. Smoking showed a statistically significant influence on carboxyhemoglobin level in mothers and newborns, and on cadmium concentration in maternal blood. In addition, low-birth-weight newborns and smoking mothers were associated. A slight but statistically significant effect of environmental pollution by lead (greater in urban/industrial populations and least in rural populations) on lead uptake by the pregnant mothers and its transfer to their fetuses was demonstrated. Some of these results suggest that during pregnancy, lead could be mobilized from maternal tissue deposits, but more work is required to confirm this hypothesis. No significant relationships were found among the other epidemiological parameters and the biological measurements made on maternal and cord blood.^ieng

Placental transfer of lead, mercury, cadmium, and carbon monoxide in women. I. Comparison of the frequency distributions of the biological indices in maternal and umbilical cord blood.

PIP: 500 pregnant women living in different areas in Belgium were surveyed to evaluate the extent of environmental exposure to heavy metals (lead, cadmium, and mercury) during fetal life, possible biological effects of such exposure, and various epidemiological significances which may influence such exposure. In addition carboxyhemoglobin level was determined. And frequency distributions of these various hematological indexes were compared. Maternal and umbilical cord blood levels of these hematological parameters indicate that the 3 metals do cross the placenta, but the transfer rate differs for each heavy metal. No barrier was demonstrated for mercury transfer. A slight barrier seemed present for lead. A barrier of some importance was demonstrated for cadmium. Statistical correlations bear out these contentions; there was a lower correlation between maternal blood cadmium and umbilical blood cadmium concentrations (r + .38) than for the other 2 metals (r .6). Carboxyhemoglobin levels of mother and newborn are highly correlated (P .001), and in mothers carboxyhemoglobin levels are also associated with cadmium concentration in blood, suggesting that the source of these pollutants is the same, namely smoking. There were no significant correlations observed between blood lead concentrations and erythrocyte prophyrin level; rather, because of its high sensitivity to lead, the erythrocyte enzyme ALAD was negatively correlated with blood lead in mother and newborn.^ieng

Impact of air pollution by lead on the heme biosynthetic pathway in school-age children.

Blood-lead level (Pb-B), erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity, free erythrocyte porphyrin (FEP) concentration, delta-aminolevulinic acid concentration in urine (ALAU), hematocrit value, and hemoglobin concentration were compared for groups of children 10-13 years old from areas differently polluted by lead (rural area and lead smelter area). The biological responses of the children were also compared with those observed in adults similarly exposed to lead (Pb-B: 10-40 mug/100 ml). Compared with the rural children, children living less than 1 km from the smelter exhibited a significant increase of Pb-B and FEP, a significant inhibition of ALAD, and a slight positive correlation of ALAU with Pb-B; however, they showed no biological signs of anemia. In children living approximately 1.5 km from the smelter, there was still a significant increase of Pb-B and a concomitant inhibition of ALAD, but no change in FEP concentration. Comparison of the dose-response curves between Pb-B and FEP in adult males, adult females, and children indicates that the sensitivity to lead is in the order of children larger than or equal to women greater than men. Based on the FEP response, it is proposed that 25 mug Pb/100 ml blood be regarded as the maximum biologically allowable concentration of lead in blood of school-age children.

Effect of lead on some parameters of the heme biosynthetic pathway in rat tissues in vivo.

Lead was administered to male and female rats in drinking water for 3 and 6 weeks at the following doses: 0, 10, 100, 1000, 5000 ppm and for 6 months at 10 ppm only. Various parameters of blood - lead concentration (Pb-B), hematocrit (Htc), hemoglobin (Hb), free erythrocyte porphyrins (FEB), delta-aminolevulinate dehydratase (ALAD), reticulocytes - and tissue - ALAD, free tissue porphyrins (FTP), lead concentration (Pb-T) - were determined. Pb-B increases with dose but reaches rapidly a plateau despite continuous Pb administration. Concentration of Pb in kidney, liver and brain correlates with Pb-B. Pb does not accumulate in heart. Kidney is the main site of Pb deposition and kidney ALAD is the parameter most susceptible to lead, since reduction is observed in all treated groups after 3 weeks of exposure. However, kidney ALAD inhibition is transitory since after 6 weeks it is only observed in the 5000 ppm group. At 10 ppm lead prevents also the increase in blood ALAD activity normally associated with the reticulocytosis of repetitive bleeding. The next parameters affected by lead are: ALAD in blood which is inhibited after 6 weeks of treatment with 100 ppm lead, and FEP, delta-aminolevulinic acid plus other pyrrole-forming substances in urine (ALA-U), and FTP in kidney which are increased after 3 or 6 weeks of treatment with 1000 and 5000 ppm lead.

Effect of short-term administration of lead to pregnant rats.

Lead was administred to adult female rats in drinking water (0;0.1:1 and 10 ppm) for 3 weeks before mating, during pregnancy and during 3 weeks after delivery. On day 21 after delivery the mothers and their newborns were sacrified and various parameters of blood -- lead concentration on (Pb-B), hematocrit (Htc), hemoglobin (Hb), free erythrocyte porphyrins (FEP), delta0aminolevulinate dehydratase (ALAD) -- and tissue -- ALAD, free tissue porphyrins (FTP), lead concentration (Pb-T) -- were determined. In mothers a significant increase in Pb-B and Pb concentration in kidney was found in the 10 ppm group, but this increase in lead concentration was not associated with any statistically significant modification of the biochemical parameters. In newborns, lead concentration in blood and in kidney was also significantly increased in the 10 ppm group and this lead exposure was associated with a decrease of the ALAD activity in blood and an increase of FTP in kidney. On the basis of the biochemical parameters investigated one can therefore conclude that the developing organism is more susceptible to the biological action of lead than the organism of adult animals and that the "no-effect" level of lead administered during pregnancy and in the neonatal period is around 1 ppm.