Severe skin and soft tissue infection in cohort patients admitted in a teaching hospital in Belgium: identification of risk factors for surgery.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are associated with significant mortality if not promptly diagnosed and surgically treated. AIM: This study aims to compare patients with severe skin and soft tissue infection treated with or without a surgical intervention and to identify risk factors that can predict the need for early surgery. METHODS: Demographics, clinical, laboratory, Risk Indicator for Necrotizing Fasciitis (LRINEC) and imaging results were retrospectively collected. RESULTS: There were 91 non-NSTI (group 1), 26 NSTI who were operated (group 2) and eight suspected NSTI who were not operated (group 3). In the multivariate analysis, skin necrosis, tachycardia, CRP value and hyperglycemia were predictive for surgery. A performance analysis revealed AUC of 0.65 (95%CI: 0.52-0.78) as to the LRINEC score for the use of surgery. The AUC for a predictive model associating four variables (heart rate, skin necrosis, CRP and glycemia at admission) was 0.71 (95%CI: 0.59-0.84). In terms of outcome, the median length of stay (LOS) was statistically higher in group 2 vs. group 1 (seven days (5-15) vs. 34 days (20-42), p < .001) and in group 2 vs. group 3 (34 days (20-42) vs. 14 days (11-19), p = .005). The overall in-hospital mortality at 30 days was 3.2% and did not statistically differ between the three groups. CONCLUSIONS: Although the LRINEC score performed well in predicting surgery, the AUC of a model combining four predictive variables (glycemia, skin necrosis, CRP and heart rate) was superior. Further research is needed to validate this model.

Exceptional manifestation of Madelung's disease after liver transplantation.

Unlike simple obesity, Madelung's disease (MD) is a rare disease characterized by symmetric accumulation of massive adipose tissue on the neck, the superior part of the trunk and limbs, leading to a pathognomonic cosmetic deformity. Here, we report an extremely rare case of MD associated with bilateral gynecomastia in a 61-year-old man, with a history of recent liver transplantation for alcoholic liver disease (ALD).

Effects of delayed mating on the reproductive biology of the vine mealybug, Planococcus ficus (Hemiptera: Pseudococcidae).

The effect of increasing mating delay on the reproductive performance and population growth rates of the vine mealybug, Planococcus ficus (Signoret) (Hemiptera: Pseudococcidae), was investigated under laboratory conditions. Virgin females were mated at 1, 3, 5, 7, 14, 21 and 28 days after emergence and reproductive and life table parameters were estimated. The pre-oviposition period (number of days between mating and the onset of oviposition) significantly decreased in females mated within 7 days, whereas females mated at older ages showed equivalent pre-oviposition periods (7 days, as shorter delays in mating did not reduce the population growth rates.

[Pediatric lower extremity reconstruction]. / Reconstruction des traumatismes complexes des membres inférieurs chez l'enfant.

Lower limb multi-tissular injuries are rare in children but require elaborate surgical care considering the child's growth potential, donor-site morbidity and the psychological consequences for the child and his family. This review outlines the various coverage options, from simple to more complex, developing their principles and their results. Technical features of wound repair of the lower limb in children will be detailed. An efficient and ambitious care can give excellent functional outcomes in children, even when extended, multi-tissue lesions members are involved.

Sleep and primary headaches.

The relationship between sleep and primary headaches has been known for over a century, particularly for headaches occurring during the night or early morning. Migraine, tension-tyre headache, and cluster headache may cause sleep fragmentation, insomnia, and hypersomnia, causing considerable social and economical costs and several familial problems. By contrast, sleep disorders may themselves trigger headache attacks. Finally, headaches and sleep disorders can also be symptoms of other underlying pathologies. Despite this background, there is still no clarity about the mechanism that links these two entities and their interdependence remains to be defined. Patients with primary headache should undergo a careful assessment of sleep habits.

In vivo evaluation of type 2 transglutaminase contribution to the metastasis formation in melanoma.

One of the most relevant problems in tumour treatment resides on the ability of the tumour to form metastasis and disseminate among the organism. The formation of metastases is a complex process, which requires the action of various effectors, not yet completely identified. The analysis of various types of tumours revealed a complex picture about the relationship between type 2 transglutaminase (TG2) expression and outcome and/or metastatic potential of the tumour itself. In some tumours, the transition to a highly invasive state is paralleled by an up-regulation of TG2 expression and/or activity while in some other a down-regulation has been reported. In addition, host tissues seem to react to tumour invasion by up-regulating TG2 expression. In order to analyse whether TG2 might be involved in the metastatic process in melanoma, we studied the metastases formation and development by means of the B16-F10 murine melanoma cell line and with TG2(-/-) mice as experimental model. Our results indicate that TG2 absence in the host is a favouring condition for the formation and development of the metastasis, while the presence of TG2 in the tumour's cell might be requested for the development of the metastasis.

Role of transglutaminase 2 in quercetin-induced differentiation of B16-F10 murine melanoma cells.

Flavonoids belong to the class of plant polyphenolic compounds with over 6,000 individual structures known. These phytochemicals have attracted the interest of the scientists, because they possess a remarkable spectrum of biological activities, such as antiallergic, antiinflammatory, antioxidant, antimutagenic and anticarcinogenic. In this work, we compared the anticancer potential of two flavonoids, quercetin and pelargonidin, on highly metastatic B16-F10 melanoma murine cells. We have evaluated different parameters related to cell proliferation and differentiation, such as cell number, toxicity, intracellular content of polyamines and transglutaminase (TG, EC 2.3.2.13) activity. The higher inhibition of tumor cell growth, with respect to control, was obtained with quercetin cell treatment, i.e. 32% reduction after 48 h and 39% reduction after 72 h of incubation (P < 0.001). In parallel, quercetin-treated cells showed a similar decrease in polyamine content. TG activity was fourfold increased, with respect to control, after 48 h and twofold increased after 72 h (P < 0.001). Pelargonidin treatment did not show significant antiproliferative effects and any increase in TG activity. Proteomic approach was used to investigate changes in protein expression profiles in tumor cells following quercetin treatment. Changes in expression of 60 proteins were detected, i.e. 8 proteins were down-regulated, 35 up-regulated, 11 "de novo" synthetized proteins and 6 suppressed proteins were present in treated cells. A 80 kDa spot, identified as TG type 2 by Western blot analysis, presented a fourfold increase in intensity, confirming the key role played by TG in the induction of cancer cell differentiation.

Protein-polyamine conjugates by transglutaminase 2 as potential markers for antineoplastic screening of natural compounds.

The role of post-translational modification of cell proteins with polyamines, a reaction catalyzed by a tissue tranglutaminase (TG, EC 2.3.2.13), in the induction of cell differentiation, represents an intriguing strategy to control cell proliferation and metastatic ability of different tumor cell lines. In this review, we focus our attention on the metabolic aspects of some natural compounds (methylxantines, retinoids and flavonoids) responsible of their antitumor effects exerted through the induction of TG activity in cancer cells.

Impairment of the metastatic activity of melanoma cells by transglutaminase-catalyzed incorporation of polyamines into laminin and Matrigel.

Previously published evidences highlighted the effect of transglutaminase (TG, EC 2.3.2.13) activation on the reduction of the in vitro adhesive and invasive behaviour of murine B16-F10 melanoma cells, as well as in vivo. Here, we investigated the influence of spermidine (SPD) incorporation by TG into basement membrane components i.e. laminin (LN) or Matrigel (MG), on the adhesion and invasion of B16-F10 melanoma cells by these TG/SPD-modified substrates. The adhesion assays showed that cell binding to the TG/SPD-modified LN was reduced by 30%, when compared to untreated LN, whereas the reduction obtained using TG/SPD-modified MG was 35%. Similarly, tumor cell invasion by the Boyden chamber system through TG/SPD modified LN or MG was respectively reduced by 45%, and by 69%. Evaluation of matrix metalloproteinase (gelatinases MMP-2 and MMP-9) activities by gel-zymography showed that MMP-2 activity was unaffected, while MMP-9 activity was reduced by about 32% using TG/SPD-modified substrate. These results strongly suggest that the observed antiinvasive effect of TG activation in the host may be ascribed to the covalent incorporation of polyamines, which led to the post-translational modification of some components of the cell basement membrane. This modification may interfere with the metastatic property of melanoma cells, affecting the proteolytic activity necessary for their migration and invasion activities.

Cryptogenic cerebral infarction in a young patient with very high lipoprotein(a) serum level as the only risk factor.

Lipoprotein(a) [Lp(a)] is a plasma lipoprotein that consists of a low-density lipoprotein (LDL)-like particle containing APO B-100 and apolipoprotein(a), linked by a disulphide bridge. There is evidence that higher serum level of Lp(a) is a predictor of various vascular diseases, such as myocardial infarction, coronary stenosis, re-occlusion of aortocoronary bypass vein grafts, peripheral atherosclerosis and cerebral infarction [1-4]. We describe a young man with a cryptogenic stroke with very high serum level of Lp(a) as the only vascular risk factor.

Atherosclerotic adult Moya-Moya disease in a patient with hyperhomocysteinaemia.

Moya-Moya is a rare cerebrovascular occlusive disease characterized by bilateral stenosis or occlusion at the terminal portion of the internal carotid artery and abnormal vascular network at the base of the brain, named "moya-moya". In children, Moya-Moya disease usually presents with ischemic cerebrovascular events, mainly TIA or lacunar stroke, leading to mental deterioration. In adults, especially in females, it presents with intracranial haemorrhages. We describe the case of an adult patient with an atherosclerotic Moya-Moya disease which presented with a cerebral borderzone infarction.

Role of the FAD-dependent polyamine oxidase in the selective formation of N(1),N(8)-bis(gamma-glutamyl)spermidine protein cross-links(1).

Protein-bound gamma-glutamylpolyamines have highlighted a new pathway in polyamine metabolism. Human foreskin keratinocytes offer a suitable model for this study. Indeed, they develop polymerized envelopes, as they differentiate, rich in epsilon-(gamma-glutamyl)lysine and N(1),N(8)-bis(gamma-glutamyl)spermidine cross-links. We have found that the selective oxidation of N(1)-(gamma-glutamyl)spermidine and N-(gamma-glutamyl)spermine by FAD-dependent polyamine oxidase (PAO) may be one of the cellular mechanisms regulating the preferential formation of a sterically defined bis(gamma-glutamyl)spermidine cross-link. The significance of this finding is unknown, but it suggests that the target of this PAO-modulation is to achieve the biochemical prerequisite for production of a normal epidermal stratum corneum.

Enhancement of transglutaminase activity and polyamine depletion in B16-F10 melanoma cells by flavonoids naringenin and hesperitin correlate to reduction of the in vivo metastatic potential.

The in vitro and in vivo effects of two flavonons, naringenin (NG) and hesperitin (HP) on the proliferation rate of highly metastatic murine B16-F10 melanoma cell were investigated. NG or HP treatment of melanoma cells produced a remarkable reduction of cell proliferation, paralleled with both the lowering of the intracellular levels of polyamine, spermidine and spermine and the enhancement of transglutaminase (TGase, EC 2.3.2.13) activity. Orally administered NG or HP in C57BL6/N mice inoculated with B16-F10 cells affected the pulmonary invasion of melanoma cells in an in vivo metastatic assay. The number of lung metastases detected by a computerized image analyzer was reduced, compared to untreated animals, by about 69% in NG-treated mice and by about 36% in HP-treated mice. Survival studies showed that 50% of the NG-treated animals died 38 +/- 3.1 days after tumor cell injection (control group: 18 +/- 1.5 days) and HP-treated mice died 27 +/- 2.3 days after cell inoculation. Taken together, these findings provide further evidences for the potential anticancer properties of dietary flavonoids as chemopreventive agents against malignant melanoma.

Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice.

The administration of mineral sulphur water is an alternative experimental approach for the treatment of rheumatic diseases, such as osteoarthritis (OA), that cause the degeneration of bone and cartilage and sufferance to the patients. Chondroitin sulfate (CS) is a symptomatic slow acting nutropeucital agent currently used in molecular therapy of OA. Therefore, we have studied the role and efficacy of the selective soil paste from the mineral sulphur enriched spring (mud)-therapy alone or in combination with CS in the treatment of OA. The study was performed on 40 C57 Black 6N mice, an experimental model which spontaneously develop an osteoarthritic process. The animals were divided in 4 groups and were treated with the single agents or with the combination. After 30 days of treatment all the mice were sacrificed and right knees and blood were collected. It was found that CS determined a reduction of radiological and histological features of chondrodegeneration and that mud-therapy increased the effects of CS in the animal group treated with the combination. However, the effects of thermal therapy alone were not statistically significant. Since OA is characterized by an increase of the production of nitric oxide (NO) by chondrocytes in extracellular matrix with its consequent elevation in serum and synovial fluid, we have evaluated the effects of the treatments on serum NO levels. CS alone induced a statistically significant reduction of NO serum levels (90+/-13 micromM vs 219+/-60 microM of control group, P<0.05) while mud-therapy alone induced a not statistically significant reduction of serum NO (170+/-62 microM, P>0.05). However, the latter strongly potentiated the decrease of serum NO induced by CS (31+/-1.5 microM) with a high statistical significance if compared to both the control group (P<0.01) and the CS-treated group (P<0.05). In conclusion, this study demonstrates that mud-therapy with sulphur mineral water could represent an important phase of the therapeutic strategy of OA. This experimental strategy could integrate and potentiate the standard pharmacological tools. Moreover, we have set a valid experimental in vivo model for the study of the thermal effects on the development of OA.

Apolipoprotein E polymorphism and stroke subtypes in an Italian cohort.

BACKGROUND: Studies have indicated that apolipoprotein E (ApoE)-epsilon4 is a risk factor for ischemic cerebrovascular diseases (ICVD), but the existence of this association is still controversial. The aims of this study were: (1) to compare ApoE genotype and allele frequencies in Italian cases with ICVD and in healthy control subjects and (2) to compare ApoE allele frequencies among ischemic stroke subtypes. METHODS: A hospital-based cohort of 302 Italian subjects with ICVD and 228 healthy subjects have been recruited to investigate the role of ApoE polymorphisms as risk factors for ICVD. TOAST criteria were employed to stratify ICVD cases by subtypes. RESULTS: No significant differences in ApoE genotype and allele frequencies were found between cases and control subjects. The frequency of ApoE-epsilon4 was lower in cases than in control subjects (6% vs. 10.1%), although not significantly. No differences in ApoE genotype and allele frequencies were evident among ICVD subtypes. However, out of 36 ApoE-epsilon4 alleles 23 (3.7%) were found in subjects with ICVD related to primary degenerative arterial disease related to large vessel disease and small vessel disease, and 13 (2.1%) in remaining subjects. Using logistic regression analysis we assessed whether ApoE-epsilon4 allele was independently associated with risk of ICVD related to a primary degenerative arterial disease compared to other ICVD subtypes. While classical risk factors were significantly associated with higher risk for ICVD due to large vessel disease and small vessel disease than other ICVD subtypes, the role of ApoE-epsilon4 allele was not significant (OR 1.25, 95% CI 0.57-2.74). CONCLUSION: Our study shows similar ApoE-epsilon4 genotype and allele frequencies in patients with ICVD and in control subjects. No differences were found among different ICVD subtypes either.

Restricted pain and thermal sensory loss in a patient with pontine lacunar infarction: a clinical MRI study.

Pure sensory syndrome (PSS) is characterized by hemisensory symptoms without other major neurological signs. It was initially attributed to thalamic lacunar infarction, but several reports have shown the PSS can be due to small infarcts involving the posterior part of the internal capsula, the cerebral cortex and the brainstem. Paramedian and lateral pontine infarctions are associated respectively with lemniscal and spinothalmic (ST) sensory impairment. We describe a patient with an isolated impairment of the ST modalities caused by a segmental paramedian pontine infarction.

Interleukin-18 (IL-18) and matrix metalloproteinase-9 (MMP-9) in post-menopausal osteoporosis.

This survey covered 60 post-menopausal women with osteoporosis. The patients were divided into three equal groups, and each group was treated with one of the three so-called anti-resorptive drugs, namely alendronate (10 mg/day) risedronate (5 mg/day) and raloxifene (60 mg/day) for 12 months. The Elisa technique was used to measure circulating IL-18 and MMP-9. Lumbar bone mineral density (BMD) levels were determined by using dexa mineralometry (Lunar DPX) at baseline and after 12 months of treatment. The results showed comparable responses of the patients treated with alendronate or risedronate, being a significant increase in BMD, an increase in circulating IL-18, and only slight modifications in circulating MMP-9 levels. After 12 months of treatment with raloxifene, there were minimal, non-significant increases in BMD, slight modifications in IL-18 levels, and a significant reduction in circulating MMP-9 levels. The conclusions can be drawn that all three drugs, albeit through different mechanisms, can be considered valid treatments for post-menopausal osteoporosis. Although measurements of circulating IL-8 and MMP-9 levels allowed us to differentiate the effects of the three drugs used, as of today, they have no real role in the diagnosis and/or follow-up of osteoporosis.