Toxicity and morbility after isolated lower limb perfusion in 242 chemo-hyperthermal treatments for cutaneous melanoma: The experience of the Tuscan Reference Centre

Background

The aim of this retrospective study was to assess the results concerning the regional and systemic toxicity and complications in 242 chemo-hyperthermal treatments (HILPs) for lower limb melanoma.

Patients and methods

60 HILPs (G-A) were performed with mild HT plus L-PAM (10 mg/lt) ± D-actimomycin; 74 HILPs (G-B) with true HT (40–41.8°C) plus L-PAM (10 mg/lt) ± D-act; 108 HILPs (G-C) with true HT plus L-PAM (10 mg/lt) ± D-act plus L-PAM (5 mg/lt) additional bolus.

Results

Limb toxicity was very low in G-A and in G-B; increasing toxicity (grade III = 37%) in G-C; no grade IV statistical difference was registered in all three groups, with percentage values among 1.6% and 2.7%. Systemic toxicity showed itself only in the haemopoietic parameters. No differences were registered in G-B vs G-A group. In G-C vs G-B a significative increase of systemic toxicity was seen in grade 3 (p < 0.05). Postoperative complications were acceptable. Local and systemic side-effects were transient; no permanent neurological limb deficit was registered. The postoperative mortality was recorded in 3/182 HILPs (1.6%) of the G-B and G-C groups.

Conclusion

These data suggested that the technical implementations reduced the occurrence and the severity of the side effects and complications. The essential requirement for HILP is the quality assurance of the procedures. Although higher regional and systemic toxicity were observed in the G-C group caused by L-PAM additional bolus, the safeness of the procedures under the true hyperthermal regimen and the time increase of the high L-PAM concentration have assured the treatment reliability along with the increased clinical efficacy expectations of the treatments.     

Serum C-reactive protein and cognitive function in healthy elderly Italian community dwellers

BACKGROUND: Chronic low-grade inflammation, as measured with the peripheral serum marker C-reactive protein (sCRP), may be a risk factor for dementia in elderly persons. METHODS: The relationship between sCRP and score on the Mini-Mental State Examination (MMSE), a commonly used screening cognitive measure, was investigated in 540 well functioning, healthy, and cognitively normal elders (age 73 +/- 6 years). Sociodemographic status, lifestyle, health status, traditional and nontraditional cardiovascular risk factors including plasma total homocysteine (tHcy), and other peripheral blood markers of vascular inflammation (leukocyte count, serum albumin, and plasma fibrinogen) were also assessed. RESULTS: Risk for having sCRP in the highest decile (>0.7 mg/dl) was significantly higher in individuals with MMSE score 24-25 (odds ratio = 3.07, 95% confidence interval, 1.2-7.9) and 26-28 (odds ratio = 2.10, 95% confidence interval, 1.1-3.9) compared with those scoring above 28 (reference group). Results were unaffected by adjustment for all potential confounders. No association was found between MMSE and peripheral markers of vascular inflammation other than sCRP, but lower MMSE scores were also independently associated with hyperhomocysteinemia (plasma tHcy > 15 mmol/L). CONCLUSION: In healthy, cognitively normal elderly community dwellers, increased sCRP levels are associated with concurrent cognitive impairment as measured by MMSE. The association is independent of sociodemographic status, lifestyle, health status, and traditional and nontraditional cardiovascular risk factors including hyperhomocysteinemia. Results support the hypothesis that chronic low-grade inflammation may be involved in age-related cognitive impairment.     

Chlamydia pneumoniae infection in HIV-positive patients: prevalence and relationship with lipid profile

OBJECTIVES: The aims of this study were to evaluate the prevalence and impact of Chlamydia pneumoniae infection in HIV-positive patients and to establish the relationship between C. pneumoniae infection and lipid profile. METHODS: Detection of C. pneumoniae was by polymerase chain reaction (PCR) on Peripheral Blood Mononuclear Cells (PBMCs) collected from 97 HIV-positive patients. Samples were collected after overnight fast in EDTA-treated tubes. On the same day, patients were also tested for routine chemistry, HIV viral load, CD3, CD8 and CD4 cell counts and lipid profile [cholesterol, high-density lipoproteins (HDLs), low-density lipoproteins (LDLs) and triglycerides]. RESULTS: The overall prevalence of C. pneumoniae was 39%. The prevalence of C. pneumoniae was inversely related to the CD4 lymphocyte count (P=0.03). In the naive group, C. pneumoniae-positive patients had both significantly higher HIV load (71 021+/-15 327 vs. 14 753+/-14 924 HIV-1 RNA copies/mL; P=0.03) and lower CD4 cell count (348.0+/-165.4 vs. 541.7+/-294.8; P=0.04) than C. pneumoniae-negative patients. Moreover, treatment-naive patients with C. pneumoniae infection had significantly higher mean levels of cholesterol (185.3+/-56.2 vs. 124.8+/-45.9 mg/dL; P=0.01), triglycerides (117.2+/-74.7 vs. 68+/-27.6 mg/dL; P=0.04) and LDL (122.4+/-60.1 vs. 55.6+/-58 mg/dL; P=0.05) than C. pneumoniae-negative patients. CONCLUSIONS: These data indicate that, in HIV-positive subjects, C. pneumoniae infection is relatively frequent and is associated with both low CD4 cell count and high HIV load. Furthermore, C. pneumoniae appears to be associated with hyperlipidaemia and might therefore represent a further risk factor for cardiovascolar disease in HIV-positive patients.     

Effect of adhesive properties of buffy coat on the quality of blood components produced with Top & Top and Top & Bottom bags

BackgroundThe Transfusion Medicine Unit of Reggio Emilia currently collects whole blood using conventional quadruple Fresenius Top & Top bags. In this study, new Fresenius Top & Bottom bags were assessed and compared to the routine method with regards to product quality and operational requirements.ResultsCompared to the traditional system, the whole blood units processed with Top & Bottom bags yielded larger plasma volumes (+5.7%) and a similar amount of concentrated red blood cells, but with a much lower contamination of lymphocytes (−61.5%) and platelets (−86.6%). Consequently, the pooled platelets contained less plasma (−26.3%) and were significantly richer in platelets (+17.9%).DiscussionThis study investigated the effect of centrifugation on the adhesiveness of the buffy coat to the bag used for whole blood collection. We analysed the mechanism by which this undesirable phenomenon affects the quality of packed red blood cells in two types of bags. We also documented the incomparability of measurements on platelet concentrates performed with different principles of cell counting: this vexing problem has important implications for biomedical research and for the establishment of universal product standards. Our results support the conclusion that the Top & Bottom bags produce components of higher quality than our usual system, while having equal operational efficiency. Use of the new bags could result in an important quality improvement in blood components manufacturing.     

A new therapeutic approach to erectile dysfunction: urotensin-II receptor high affinity agonist ligands

Urotensin-II (U-II) is a cyclic peptide that acts through a G protein-coupled receptor (urotensin-II receptor [UTR]) mainly involved in cardiovascular function in humans. The urotensinergic system is also implicated in the urogenital tract. Indeed, U-II relaxes human corpus cavernosum strips and causes an increase in intracavernous pressure (ICP) in rats. In light of this, the U-II/UTR pathway can be considered a new target for the treatment of erectile dysfunction. On this hypothesis, herein we report on two new UTR high affinity-agonists, P5U (H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH) and UPG84(H-Asp-c[Pen-Phe-DTrp-Orn-(pNH₂) Phe-Cys]-Val-OH). The effects of P5U and UPG84 were each compared separately with U-II by monitoring the ICP in anesthetized rats. Intracavernous injection of U-II (0.03–1 nmol), P5U (0.03–1 nmol) or UPG84 (0.03–1 nmol) caused an increase in ICP. P5U, in particular, elicited a significant increase in ICP as compared to U-II. The observed effect by using P5U at a dose of 0.1 nmol per rat was comparable to the effect elicited by U-II at a dose of 0.3 nmol. Moreover, UPG84 at the lowest dose (0.03 nmol) showed an effect similar to the highest dose of U-II (1 nmol). Furthermore, UPG84 was found to be more effective than P5U. Indeed, while the lowest dose of P5U (0.03 nmol) did not affect the ICP, UPG84, at the same dose, induced a prominent penile erection in rat. These compounds did not modify the blood pressure, which indicates a good safety profile. In conclusion, UPG84 and P5U may open new perspectives for the management of erectile dysfunction.     

Immunohistochemical expression of cell-cycle proteins in gastric precancerous lesions

Background: The early indicator for the subject predisposed to gastric cancer is abnormal proliferation of gastric epithelial cells, such as atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia, which have been considered as precancerous lesions of gastric cancer. To determine whether p53 protein, cyclins D1, and D3, and p27^kip1 play a role in the carcinogenesis pathway of gastric cancer, we performed an immunohistochemical study of their expression in gastric precancerous lesions. Methods: A total of 1 45 endoscopic gastric biopsy specimens of AG, IM, and gastric dysplasia were studied. These molecular markers were localized by immunohistochemistry. Results: P53 was expressed in 15% of cases with gastric dysplasia and not in the pre‐dysplastic stages of the gastric mucosa. All cases were concerning high‐grade dysplasia. Cyclin D1 protein was almost undetectable in the precancerous lesions of gastric cancer. Cyclin D3 protein overexpression was seen in 10% of biopsies with IM, and 50% of biopsies with gastric dysplasia. High expression of p27^kip1 protein was demonstrated in all cases of chronic gastritis. As atrophy, IM, and dysplasia develop, expression of p27^kip1 protein is suppressed. In total, 15% of dysplastic cases showed no expression of p27^kip1 protein. Conclusions: (i) P53 mutation must be a late event during the development of gastric cancer. (ii) Cyclin D1 protein overexpression may not play a role in the progression from normal to neoplastic gastric mucosa, while overexpression of cyclin D3 is an earlier event during gastric carcinogenesis, and its role must be further evaluated. (iii) Reduced expression of p27^kip1 is a rather early event in gastric tumorigenesis, before dysplastic changes occur.