A Mathematical Realization of Entropy through Neutron Slowing Down.

The slowing down equation for elastic scattering of neutrons in an infinite homogeneous medium is solved analytically by decomposing the neutron energy spectrum into collision intervals. Since scattering physically smooths energy distributions by redistributing neutron energy uniformly, it is informative to observe how mathematics accommodates the scattering process, which increases entropy through disorder.

Fatal early peripheral post-reperfusion syndrome and the role of cutaneous signs.

The purpose of this report is to present the case of a 75-year-old male affected by right common femoral artery and abdominal aortic aneurysms. His clinical history was also characterised by post-ischaemic cardiomyopathy, arterial hypertension, chronic respiratory disease and peripheral arterial disease. We performed two surgical procedures: right femoral aneurysmectomy and femoro-femoral bypass and subsequently a femoro-femoral crossover bypass plus right femoro-popliteal bypass below the knee. The second operation became necessary in order to treat acute occlusion of the right iliac-femoral arterial axis. The patient developed a progressive and aggressive lower limb post-perfusion syndrome associated to frank peripheral oedema, myocardial stunning, reperfusion arrhythmias, renal failure and respiratory distress. Cutaneous alterations (oedema of the leg, mottled skin and cyanosis of the foot) were more specific compared with Doppler ultrasound that showed the presence of adequate blood flow in the early phase. On the basis of this experience and of pertinent literature, this study represents a challenge for the understanding of the exact mechanism of origin and progression of post-reperfusion syndrome.

Extracellular matrix assessment of infected chronic venous leg ulcers: role of metalloproteinases and inflammatory cytokines.

Chronic venous ulcer (CVU) represents a dreaded complication of chronic venous disease (CVD). The onset of infection may further delay the already precarious healing process in such lesions. Some evidences have shown that matrix metalloproteinases (MMPs) are involved and play a central role in both CVUs and infectious diseases. Two groups of patients were enrolled to evaluate the expression of MMPs in infected ulcers and the levels of inflammatory cytokines as well as their prevalence. Group I comprised 63 patients (36 females and 27 males with a median age of 68·7 years) with infected CVUs, and group II (control group) comprised 66 patients (38 females and 28 males with a median age of 61·2 years) with non-infected venous ulcers. MMP evaluation and dosage of inflammatory cytokines in plasma and wound fluid was performed by means of enzyme-linked immunosorbent assay test; protein extraction and immunoblot analysis were performed on biopsied wounds. The first three most common agents involved in CVUs were Staphylococcus aureus (38·09%), Corynebacterium striatum (19·05%) and Pseudomonas aeruginosa (12·7%). In this study, we documented overall higher levels of MMP-1 and MMP-8 in patients with infected ulcers compared to those with uninfected ulcers that showed higher levels of MMP-2 and MMP-9. We also documented higher levels of interleukin (IL)-1, IL-6, IL-8, vascular endothelial growth factor and tumour necrosis factor-alpha in patients with infected ulcers with respect to those with uninfected ulcers, documenting a possible association between infection, MMP activation, cytokine secretions and symptoms. The present results could represent the basis for further studies on drug use that mimic the action of tissue inhibitors of metalloproteinases in order to make infected CVU more manageable.

Cilostazol prevents foot ulcers in diabetic patients with peripheral vascular disease.

Diabetic patients are at high risk of foot ulcerations that may lead to limb amputations with important socio-economic impact. Peripheral vascular disease may be frequently associated in diabetes mellitus type II with its main symptom, intermittent claudication. Many studies reported the known efficacy of cilostazol in treating vascular claudication. Metalloproteinase-9 (MMP-9) seems to be a biochemical marker implicated in chronic wounds and in particular in diabetic foot ulcers. Cilostazol appears to have a lowering effect on MMP-9 levels and this may suggest a beneficial effect in order to prevent or retard the onset of foot ulcer in diabetic patients. In our study, two groups of diabetic patients with peripheral vascular disease were divided into two groups according to the presence of claudication in order to receive cilostazol. Group A (31 patients without claudication) were not eligible to receive cilostazol whereas Group B (47 patients with claudication) received cilostazol administration for 24 weeks (100 mg orally twice daily). Median follow up was of 16 months. During the follow up, 4·25% of patients of Group B and 35·48% of patients of Group A (P < 0·01) showed onset of foot ulceration. Although further randomised and controlled studies are required cilostazol seems to show beneficial effects for primary prevention of diabetic foot ulcers.

Low molecular weight heparin improves healing of chronic venous ulcers especially in the elderly.

Venous ulcers are common, especially in the elderly, accounting for more than 50% of all lower extremity ulcers with important socioeconomic problems. Improving extracellular matrix functioning, by heparin administration, seems to be a way to support wound healing. A total of 284 patients with venous ulcers were recruited in a 4-year period. All patients were subjected to the most appropriate treatment after considering their preference (compression therapy followed or not by vein surgery). Patients were randomised into two groups of 142 persons in each (group A and group B as cases and controls, respectively). Patients of group A, in addition to the basic treatment as described earlier, received administration of nadroparin 2850 IU/0.3 ml through subcutaneous injection once a day for 12 months, whereas group B patients received basic treatment alone. Healing was assessed by means of direct ulcer tracing with computerised planimetry. Group A showed a healing rate of 83·80% at 12 months, whereas that of group B was 60·56%. Results by age group surprisingly showed that the group of older patients took the most advantage from long-term treatment with low molecular weight heparin; this group also had lowest recurrence rate.

Doxycycline speeds up healing of chronic venous ulcers.

Venous ulcers are common, with an overall prevalence of up to 2% in the general population of western countries, and have significant socioeconomic impact. Matrix metalloproteinases (MMPs) are involved in the alteration of extracellular matrix that could lead to venous ulceration. Sixty-four patients with venous ulcers were recruited in a 22-month period. All patients were subjected to the most appropriate treatment considering also the patient's wishes (compression therapy followed or not by vein surgery). Patients were randomised into two groups of 32 persons in each (groups A and B). Patients of group A in addition to the basic treatment, described above, received the administration of oral low doses of doxycycline 20 mg b.i.d. for 3 months, whereas patients of group B received basic treatment only. Healing was assessed by means of direct ulcer tracing with computerised planimetry. Group A showed a higher healing rate compared with group B. In group B, the lower healing rate was related to higher levels of MMP-9; neutrophil gelatinase-associated lipocalin and vascular endothelial growth factor, documented in plasma; wound fluid and biopsies executed and compared between both groups. Pharmacological treatments, as doxycycline administration, which by means of its immunomodulatory and anti-inflammatory actions, through the inhibition of MMP, could improve extracellular matrix functioning and represent a possible solution to support wound healing.

Hyperhomocysteinaemia and chronic venous ulcers.

Chronic venous ulceration (CVU) is the major cause of chronic wounds of lower extremities, and is a part of the complex of chronic venous disease. Previous studies have hypothesised that several thrombophilic factors, such as hyperhomocysteinaemia (HHcy), may be associated with chronic venous ulcers. In this study, we evaluated the prevalence of HHcy in patients with venous leg ulcers and the effect of folic acid therapy on wound healing. Eighty-seven patients with venous leg ulcers were enrolled in this study to calculate the prevalence of HHcy in this population. All patients underwent basic treatment for venous ulcer (compression therapy ± surgical procedures). Patients with HHcy (group A) received basic treatment and administered folic acid (1·2 mg/day for 12 months) and patients without HHcy (group B) received only basic treatment. Healing was assessed by means of computerised planimetry analysis. The prevalence of HHcy among patients with chronic venous ulcer enrolled in this study was 62·06%. Healing rate was significantly higher (P < 0·05) in group A patients (78·75%) compared with group B patients (63·33%). This study suggests a close association, statistically significant, between HHcy and CVU. Homocysteine-lowering therapy with folic acid seems to expedite wound healing. Despite these aspects, the exact molecular mechanisms between homocysteine and CVU have not been clearly defined and further studies are needed.

Low serum albumin level as an independent risk factor for the onset of pressure ulcers in intensive care unit patients.

Critically ill patients are at high risk of developing pressure ulcers (PUs) and patients who develop PUs remain significantly longer in the intensive care unit (ICU) with significantly increased morbidity and mortality. Therefore, the identification of patients at truly increased risk is important. The aim of this study was to examine the association of low serum albumin present at admission in ICU patients with the onset of PUs. We conducted a retrospective cohort study on 610 patients who were admitted to intensive care unit. Level of serum albumin and other biochemical indices, recorded at the time of admission, were collected. We collected information about PU occurrence after admission and conducted a statistical analysis with biomarkers at ICU admission and during hospital stay. The incidence of PU in the ICUs was 31% and about 70% of patients with PUs had hypoalbuminemia at admission. The lowest values of serum albumin in patients with PUs were directly proportional to the severity of ulcers. In this study, we found a close association between serum albumin and PUs. In fact serum albumin was negatively correlated with PU and may be considered one of the independent determinants of PU occurrence in patients admitted to ICUs.

Chronic venous leg ulcers are associated with high levels of metalloproteinases-9 and neutrophil gelatinase-associated lipocalin.

Venous ulcers are related to dysfunctions in extracellular matrix. Both matrix metalloproteinases (MMP) and neutrophil gelatinase-associated lipocalin (NGAL) could play a role in the healing process in patients with chronic venous ulcers. We evaluated the role of MMP-9 and NGAL in the healing process in venous ulceration. We performed an open-label, parallel groups, single clinical center study. Patients with chronic venous leg ulcers represented the test group (Group I), whereas patients without chronic ulcers represented the control group (Group II). In Group I plasma and wound fluid samples were collected at the time of admission, at the time of the surgery, and at the follow-up, while ulcer tissues were taken at the time of the surgery. In Group II, plasma and wound fluid were collected at admission and at the time of the surgery, whereas skin tissues were collected at the time of the surgery. Enzyme-linked immunosorbent assay test was used to evaluate the levels of MMP-9 and NGAL in plasma and wound fluid, whereas Western blot analysis was performed to estimate the expression of MMP-9 and NGAL in tissues. Enzyme-linked immunosorbent assay tests revealed significantly higher levels of MMP-9 and NGAL in both plasma and wound fluid of patients with ulcers compared to patients without ulcers (p < 0.01). Moreover, Western blot analysis documented an increased expression of MMP-9 and NGAL in biopsy tissue of patients with ulcers compared to patients without ulcers (p < 0.01). In conclusion MMP-9 and NGAL may correlate with the clinical course of venous ulcers.

Application of platelet-rich gel to enhance healing of transmetatarsal amputations in diabetic dysvascular patients.

Transmetatarsal amputation (TMA) represents an effective surgical procedure used to treat several clinical conditions such as forefoot infection, gangrene and chronic ulceration in diabetic patients. TMA permits walking without the need for prosthesis, but nevertheless is burdened with a high complications rate. The aim of this study was to evaluate the possibility to use platelet gel (PG) as an adjuvant therapy when performing TMA procedure in diabetic patients. In a 6-year period, 26 diabetic patients had undergone TMA procedure followed by autologous PG applications (group A) and 32 patients had undergone TMA as sole procedure (group B). After TMA procedure, the treatment is based on outpatient management and consists of a weekly platelet-rich plasma gel application on the surgical wound for 1 month in group A and on clinical evaluation only for group B. For group A, healing rate was of 96.15% and one patient (3.84%) presented wound dehiscence, and no postoperative wound infections occurred. For group B, healing rate was of 59.37%; severe infection of the stump prompted to the proximal amputations in 40.62% of patients during the follow-up period. PG application may be an effective adjuvant treatment to improve wound healing in diabetic dysvascular patients.

A genetic study of chronic venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is an important cause of morbidity in Western countries. The aim of this study is to demonstrate the heredity of CVI, focusing on molecular and genetic aspects of the disease. METHODS: The study depended on the recruitment of informative families, accurate determination of the phenotype of each family member, and blood sample for DNA extraction for genetic analysis. Each family member was invited to attend a vascular consultation. A genealogical tree for each recruited family was composed. Then, a peripheral blood sample for DNA extraction from each member of the recruited families was obtained for genetic evaluation. RESULTS: By the evaluation of genealogical trees, it was evident that CVI segregates, in all families studied, in an autosomal dominant mode with incomplete penetrance. In nine families studied, varicose veins were linked to the candidate marker D16S520 on chromosome 16q24, which may account for the linkage to FOXC2. CONCLUSION: In our study, in families with affected patients with the D16S520 marker, there was evidence of saphenofemoral junction reflux. The fact that there is linkage to a candidate marker for the FOXC2 gene suggests there is a functional variant within, or in the vicinity of, which predisposes to varicose veins. Further studies are necessary to identify genes and mechanism so as to achieve better understanding of the genetic basis of CVI.