Immunohistochemical expression of VEGF, HIF1-a, and PlGF in malignant melanomas and dysplastic nevi

We evaluated the role of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and hypoxia-inducible factor 1-a (HIF1-a) in melanoma angiogenesis and investigated their expression in dysplastic nevi, as potential melanoma precursors. In addition, we examined a possible correlation of VEGF expression with PlGF and HIF1-a. These factors were detected immunohistochemically in 95 melanomas of all types and stages and in 28 dysplastic nevi. We used 10 intradermal melanocytic nevi as controls. HIF1-a was expressed in 93 out of 95 (97.89%) melanomas and in none of the dysplastic or control nevi. HIF1-a expression was more intense in melanocytes around necrotic areas but did not correlate with melanoma type, the Clark staging or the Breslow thickness. A strong positive association was detected between HIF1-a and VEGF expression in all cases. VEGF was detected in 82 out of 95 (86.31%) melanomas and in 21 out of 28 (75%) dysplastic nevi, whereas it was expressed weakly in neoplastic cells of the controls. Its expression was more intense in melanomas, especially in nodular melanomas of elevated stage and thickness. PIGF was detected in 46 out of 95 (48.42%) melanomas and in none of the nevi. Expression did not correlate with melanoma staging nor thickness; however, it was more intense in superficial spreading melanomas, where a weak positive association between VEGF and PlGF was also detected. There was no association between HIF1-a and PlGF in any melanoma type. Hypoxia, through the expression of HIF1-a, plays a key role in melanoma progression; it activates VEGF secretion, which induces angiogenesis and metastasis. The role of PlGF seems to be limited.     

Benign lip lesions. A 10-year retrospective study

Objectives

This paper aims to present a retrospective analysis of a cohort of patients with benign lip lesions managed over the last decade at the Department of Maxillofacial Surgical Oncology of Theagenio Cancer Hospital of Thessaloniki. It aims to highlight the substantial clinical and histological diversity of the lesions, as well as to present an epidemiological analysis for the specific cohort/population.

Study design

During the period 1995–2004 a total of 420 patients were managed for lip lesions. Of these, 280 were malignant and 116 benign. A total of 24 cases of actinic keratosis were added in the latter group.

Results

Of the benign lesions, the commonest were haemangiomas (19.28%), actinic keratosis (17.14%), intradermal naevus (14.28%), fibroma (9.28%), papilloma (7.85%), mild and moderate dysplasia (7.85%) and mucocele (7.14%). The group included 17 different histological types of benign lesions. The most frequent site of presentation was the lower lip (56.42%). Post-operative follow-up ranged from 6 months to 2 years (average 15.5 months). There was a single case of recurrence during follow-up.

Conclusions

Benign lip lesions do not usually pose a problem for the clinician and their surgical management is straightforward. Accurate auditing and detailed statistical analysis aid in disease prevention and help avoid errors in diagnosis and management.     

Local treatment of experimental Pseudomonas aeruginosa osteomyelitis with a biodegradable dilactide polymer releasing ciprofloxacin

A biodegradable system of poly-D,L-dilactide releasing ciprofloxacin was assessed in a Pseudomonas aeruginosa osteomyelitis model after inoculation of the test pathogen into the left tibia of 76 New Zealand White rabbits; 31 were controls (group A), and 45 were implanted with the polymer at the infection site (group B). The rabbits were killed on a weekly basis, and cancellous bone was harvested for histopathology and for estimation of bacterial growth and the concentrations of ciprofloxacin. Tibial X ray was performed immediately before the animals were killed. The total number of fistulas with purulent discharge that developed after inoculation of the pathogen was counted, and fistulas with purulent discharge were found in 16 animals in group A (51.6%) and 3 animals in group B (6.7%) (P < 0.0001). The animals in group A had a profound loss of body weight compared to the animals in group B. The main radiological finding was the presence of sequestra in 25 animals (80.6%) in group A and 6 animals in group B (13.3%) (P < 0.0001). The bacterial load in group B was significantly reduced compared to that in group A, possibly due to the prolonged local antibiotic release at concentrations exceeding even 80 times the MIC for the test pathogen. The histology of animals killed after week 49 revealed a mild inflammatory reaction accompanied by diffuse fibrosis and new bone formation in group A animals and the presence of small polymer particles in group B animals. It is concluded that the system described achieved eradication of the pathogen, accompanied by clinical and radiologically confirmed benefits, so this treatment may be a candidate for the management of difficult orthopedic infections.     

Differential effects of two isoenergetic meals rich in saturated or monounsaturated fat on endothelial function in subjects with type 2 diabetes

OBJECTIVE—To examine the acute effects of consumption of monounsaturated (MUFAs) and saturated fatty acids (SAFAs) on endothelial function in subjects with type 2 diabetes.RESEARCH DESIGN AND METHODS—A total of 33 participants were examined after consumption of two different isocaloric meals: one rich in MUFA and one rich in SAFA, in the form of extra-virgin olive oil and butter, respectively. Endothelial function was assessed by determination of flow-mediated dilatation (FMD).RESULTS—FMD did not change significantly after the MUFA-rich meal but declined after the SAFA-rich meal. The FMD during the experiment, expressed as incremental area under the curve, increased after the MUFA-rich meal by 5.2 ± 2.5% and decreased after the SAFA-rich meal by 16.7 ± 6.0% (Δ = −11.5 ± 6.4%; P = 0.008).CONCLUSIONS—Consumption of an SAFA-rich meal is harmful for the endothelium, while a MUFA-rich meal does not impair endothelial function in subjects with type 2 diabetes.Endothelial dysfunction occurs early in the course of type 2 diabetes and contributes to the development of macrovascular complications of the disease (1,2). Consumption of saturated fatty acids (SAFAs) impairs endothelial function for up to 6 h postmeal (3), whereas data on the effect of monounsaturated fatty acids (MUFAs) on endothelial function in subjects with type 2 diabetes are limited. According to recent nutritional recommendations, individuals with diabetes should substitute SAFA for MUFA in their diet (4), and the predominant source of MUFA in many countries is oleic acid contained in olive oil. However, the effect of consumption of olive oil on endothelial function in subjects with type 2 diabetes is not known. We tested the hypothesis that consumption of MUFA in the form of olive oil exerts a better effect on endothelial function in subjects with type 2 diabetes than that associated with consumption of butter. Because endothelial function is affected by high blood glucose, lipid and insulin concentrations, and increased oxidative stress (2), we measured these parameters during the study.     

Association between microvessel density and histologic grade in renal cell carcinomas

Angiogenesis seems to contribute to tumor growth and the development of metastases. There may be an association between the vascular density of individual tumors and their prognosis. In the present survey we studied 53 cases of renal cell carcinoma investigating possible relationship between histologic grade and microvessel density (MVD) measured by an image analysis system. According to our results MVD was significantly associated with the histologic grade, higher grades being accompanied with a higher MVD. Further studies are needed to investigate a possible connection of MVD with the prognostic role of grade in RCCs.     

Treatment of experimental osteomyelitis by methicillin resistant Staphylococcus aureus with bone cement system releasing grepafloxacin

The authors examined the effectiveness of the local anti-microbial treatment on methicillin resistant Staphylococcus aureus (MRSA) experimental osteomyelitis. Thirty-six rabbits with chronic MRSA osteomyelitis of the right femur were treated with local grepafloxacin delivery system prepared by a mixture of acrylic bone cement (polymethyl methacrylate, PMMA) plus 4% grepafloxacin. Osteomyelitis was induced by inoculating MRSA (100 μl of cultured bacteria; 10⁷) and the local insertion of a needle, serving as a foreign body, at the upper third of the femur. The course of the infection was followed by clinical, radiographic and microbiological examination. In the third week, all animals were re-operated, needles were removed, and antibiotic containing acrylic cement was implanted. Thereafter, one control and five treated animals were sacrificed per week, within 6 weeks. Osteomyelitis was found in all rabbits. In vitro grepafloxacin levels remained high throughout the 6 weeks of the experiment. Histologically tissue reaction against the cement was not observed. Osteomyelitis lesions and bone structure were progressively repaired after cement implantation. Biomechanical analysis showed no significant influence on the mechanical properties of acrylic cement due to grepafloxacin. The above mixture could prove to be an important supplementary method for the treatment of bone infections. Such a system could replace the use of gentamycin PMMA beads in the treatment of patients with chronic osteomyelitis due to MRSA. Furthermore, the proposed method could be used as a spacer after removal septic loosened prostheses in combination with systemic administration of antibiotics.     

Association between childhood adversity and a diagnosis of personality disorder in young adulthood: a cohort study of 107,287 individuals in Stockholm County

Childhood adversity (CA) may increase the risk for later developing of personality disorder (PD). However, less is known about the association between cumulative CA and PD, and the role of childhood psychopathology and school performance. The current study examined the relationship between a range of CAs and a diagnosis of PD in young adulthood, and the roles of childhood psychopathology and school performance in this relationship. All individuals born in Stockholm County 1987–1991 (n = 107,287) constituted our cohort. Seven CAs were measured between birth and age 14: familial death, parental criminality, parental substance abuse and psychiatric morbidity, parental separation and/or single-parent household, household public assistance and residential instability. Individuals were followed from their 18th birthday until they were diagnosed with PD or until end of follow-up (December 31st 2011). Adjusted estimates of risk of PD were calculated as hazard ratios (HR) with 95% confidence intervals (CI). Associations were observed between cumulative CA and PD. During the follow-up 770 individuals (0.7%) were diagnosed with PD. Individuals exposed to 3+ CAs had the highest risks of being diagnosed with PD (HR 3.0, 95% CI 2.4–3.7). Childhood psychopathology and low school grades further increased the risk of PD among individuals exposed to CA. Cumulative CA is strongly associated with a diagnosis of PD in young adulthood. Our findings indicate that special attention should be given in schools and health services to children exposed to adversities to prevent decline in school performance, and to detect vulnerable individuals that may be on negative life-course trajectories.     

The "Palliative Care Quality of Life Instrument (PQLI)" in terminal cancer patients

Background  

This paper describes the development of a new quality of life instrument in advanced cancer patients receiving palliative care.