TNF-Based Isolated Limb Perfusion Followed by Consolidation Biotherapy with Systemic Low-dose Interferon Alpha 2b in Patients with In-transit Melanoma Metastases: A Pilot Trial

BACKGROUND: Tumor necrosis factor (TNF)-based isolated limb perfusion (ILP) yields high tumor response rates in patients with in-transit melanoma metastases. However, most patients will ultimately experience disease recurrence. The aim of this pilot study was to test the hypothesis that systemic low-dose interferon alpha-2b (LDI) might consolidate the therapeutic effect of ILP. METHODS: A total of 12 patients with in-transit melanoma metastases not amenable to surgical excision were given LDI subcutaneously (3 million IU/day, 7 days/week for 12 months) after TNF-based ILP (TNF 1 mg + melphalan (L-PAM) 10 mg/L) (group A). The clinical outcome of these patients was historically compared with that of 19 patients with similar anthropometric and disease characteristics who underwent TNF-based ILP alone (group B). RESULTS: In group A, LDI was well tolerated, only grade 2 systemic toxicity being recorded in 50% of patients. The progression-free survival analysis showed a statistically significant advantage for group A patients as compared with group B (median time to progression: 26 and 17 months, respectively; log-rank test P-value: 0.037). This survival benefit was confirmed at multivariate analysis, where treatment was the only prognostic factor retained by the prediction model. The analysis of the risk of disease progression over time suggested that this survival benefit appears to vanish after LDI discontinuation, which further strengthens the hypothesis that LDI might consolidate the therapeutic effect of TNF-based ILP. CONCLUSIONS: These preliminary findings support the conduction of larger trials to formally assess the ability of LDI to improve the clinical outcome of melanoma patients with in-transit metastases undergoing TNF-based ILP.     

Effectiveness of maternity support belts in reducing low back pain during pregnancy: a review

Aims. This article aims to review the literature published to date on the types, current use, the biomechanical effects and adverse effects of maternity support belts for low back pain during pregnancy, to identify future research directions. Background. Lumbar/pelvic support belts are frequently recommended for the prevention and treatment of low back pain during pregnancy. Design. Systematic review. Methods. MEDLINE, CINAHL, the Cochrane Library and patents databases were electronically searched. Results. Maternity support belts belong to one of the four main types of maternity support garments, which are widely commercially‐available. Current research showed limited evidence in support of the commercial maternity products regarding the effectiveness in the prevention and/or treatment of low back pain during pregnancy, other than that from the manufacturers. However, potential stabilisation effect of maternity support belt was demonstrated in some studies. Adverse effects reported include increased pain, fetal heart rate changes, skin irritation and discomfort. Conclusions. There is insufficient scientific evidence to conclude that wearing maternity support belts reduces pregnancy‐related low back pain and/or pelvic girdle pain. Future research directions in the area of biomechanics and physiology are recommended. Relevance to clinical practice. This review provides comprehensive understanding of the effectiveness of maternity support belts for the relief of low back pain during pregnancy which will facilitate healthcare professionals in providing evidence‐based advice to their patients.     

Microbiologic data overview of Italian cystic fibrosis patients

The aim of our study was to determine the frequency of microbiological culturing and prevalence of colonization by principal pathogens of the respiratory tract of Italian cystic fibrosis patients. Data on all Italian cystic fibrosis patients were collected using a questionnaire sent to all Italian CF Centers. Results were obtained of microbiological cultures from 2,521 patients. Information was gained regarding the method of gathering biological samples, the percentage of patients undergoing microbiological culturing regularly, the procedures used to isolate bacteria and types of culture media used which were selective for Burkholderia cepacia. Ninety-four percent of Italian CF patients are regularly tested microbiologically. Sputum and pharyngeal cultures are most often carried out. 49% of Italian patients are colonized by Staphylococcus aureus, 5.4% by Haemophilus influenzae, 48.9% by Pseudomonas aeruginosa and 3.8% by Burkholderia cepacia. In Italy there is a high prevalence of CF patients colonized by Staphylococcus aureus and a low prevalence of patients colonized by Haemophilus influenzae. The prevalence of Burkholderia cepacia and Pseudomonas aeruginosa does not differ significantly from other countries examined.     

Intermittent haemodiafiltration in refractory congestive heart failure: BNP and balance of inflammatory cytokines.

BACKGROUND: Elevated plasma levels of cytokines have been associated with an increased risk of congestive heart failure (CHF) even in people without history of myocardial infarction. Here we have tested the hypothesis that effective removal of pro-inflammatory cytokines in patients with advanced CHF unresponsive to diuretic treatment is associated with diuresis restoration and with a significant reduction of B-type natriuretic peptide (BNP) circulating levels. METHODS: We prospectively enrolled 10 patients with decompensated CHF (NYHA classes III-IV). Five patients unresponsive to diuretic treatment underwent a short course of intermittent haemodiafiltration (iHDF), whereas five patients responsive to diuretics were treated with intravenous boluses of furosemide. Renal function was similar between the two groups. RESULTS: Excess body fluids were removed in both groups always resulting in a reduction of pulmonary congestion and peripheral oedema. NYHA class improved in all patients, but one treated by intravenous boluses of furosemide. Only patients treated with iHDF showed a significant reduction of circulating interleukin-8 and monocyte chemoattractant protein-1. After the end of iHDF treatment, patients showed consistent restoration of diuretic responsiveness to significantly lower doses of oral furosemide up to one month of follow-up. Plasma levels of BNP before treatment were significantly higher in the iHDF group, lowering significantly in both groups after treatment. CONCLUSIONS: Our results suggest that HDF is an effective treatment for patients with advanced CHF when cytokines have to be cleared and diuretic responsiveness needs to be restored. In our experience, iHDF is a cost-effective option when compared with continuous ultrafiltration methods because it can be performed in a routine dialysis unit without adjunctive costs for machinery or personnel training.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Neurotrophin release by neurotrophins: Implications for activity-dependent neuronal plasticity

Neurotrophins, secreted in an activity-dependent manner, are thought to be involved in the activity-dependent refinement of synaptic connections. Here we demonstrate that in hippocampal neurons and the rat pheochromocytoma cell line PC12 application of exogenous neurotrophins induces secretion of neurotrophins, an effect that is mediated by the activation of tyrosine kinase neurotrophin receptors (Trks). Like activity-dependent secretion of neurotrophins, neurotrophin-induced neurotrophin secretion requires mobilization of calcium from intracellular stores. Because neurotrophins are likely to be released from both dendrites and axons, neurotrophin-induced neurotrophin release represents a potential positive feedback mechanism, contributing to the reinforcement and stabilization of synaptic connections.     

Pretreatment with bendazac attenuates retinal damage induced by intense light in rats

Bendazac is a drug which protects proteins from denaturation induced by different agents. It is also effective in protecting rabbits from X-ray-induced cataract. This study deals with the effects of bendazac on the intense light-induced retinal damage in rats. Four groups of animals received orally 0, 50, 100 or 200 mg/kg of bendazac L-lysine salt three times a day for 3 days and once the fourth day, before 1 h exposure to intense-green filtered light. Fourteen days after housing in a dark room, the rats were sacrificed and the retinae were examined by light microscopy. Retinal damage was graded according to a score severity from 0 to 5. The mean score for control animals was 2.23, whereas a dose-related and statistically significant reduction of retinal damage was detected in bendazac treated rats, i.e. 1.72, 1.54 and 1.40. A protective activity in the distribution of the severity score, i.e. a higher incidence of no damaged retinae and a lower frequency in the most severely affected ones, was also observed in treated versus control rats. These results suggest a potential therapeutic value of bendazac in the treatment of those conditions, such as retinitis pigmentosa and senile macular degeneration, in which the light exposure plays a role as a co-factor.     

Effect of domperidone on the release of insulin after intravenous glucose load in man

To determine whether the blockade of the dopaminergic system is capable of modifying glucose-induced insulin release in man, the responses of insulin to an iv glucose load were measured at various domperidone infusion rates. The infusion of 5 micrograms/kg/min of domperidone increased significantly plasma insulin levels during the acute phase of glucose-induced insulin release and lowered plasma glucose values at 50 and 60 min; the k of glucose disappearance improved significantly. At lower domperidone infusion rates the acute increment of insulin after glucose load was indistinguishable from the response observed at 5 micrograms/kg/min until 0.5 microgram/kg/min, while similar responses in control and experimental tests were observed at 0.25 microgram/kg/min. A group of subjects was submitted to an arginine load in order to establish whether the effect observed with domperidone was specific for the glucose-induced insulin release; but, this time, we did not observe any significant effect during the domperidone-induced dopaminergic blockade. Furthermore, we also measured the plasma prolactin levels, to see whether the specific and well known effect of domperidone on prolactin release matches with the effect on beta-cell function. As far as prolactin is concerned, we observed a dose response effect of domperidone infusion, with a detectable elevation of prolactin at infusion rate of 0.25 microgram/kg/min. Since domperidone is a specific antagonist of dopamine D2-receptors, we propose that dopamine might exert a specific inhibiting effect on glucose-induced insulin release through this class of dopamine receptors.     

Relationship between diet and anticoagulant response to warfarin

Background Diet composition is one of the factors that may contribute to intraindividual variability in the anticoagulant response to warfarin. Aim of the study To determine the associations between food pattern and anticoagulant response to warfarin in a group of Brazilian patients with vascular disease. Methods Recent and usual food intakes were assessed in 115 patients receiving warfarin; and corresponding plasma phylloquinone (vitamin K₁), serum triglyceride concentrations, prothrombin time (PT), and International Normalized Ratio (INR) were determined. A factor analysis was used to examine the association of specific foods and biochemical variables with anticoagulant data. Results Mean age was 59 ± 15 years. Inadequate anticoagulation, defined as values of INR 2 or 3, was found in 48% of the patients. Soybean oil and kidney beans were the primary food sources of phylloquinone intake. Factor analysis yielded four separate factors, explaining 56.4% of the total variance in the data set. The factor analysis revealed that intakes of kidney beans and soybean oil, 24-h recall of phylloquinone intake, PT and INR loaded significantly on factor 1. Triglycerides, PT, INR, plasma phylloquinone, and duration of anticoagulation therapy loaded on factor 3. Conclusions Fluctuations in phylloquinone intake, particularly from kidney beans, and plasma phylloquinone concentrations were associated with variation in measures of anticoagulation (PT and INR) in a Brazilian group of patients with vascular disease. This material is based upon work supported by CNPq and by federal funds from the U.S. Department of Agriculture, Agricultural Research Service under Cooperative Agreement No. 58-1950-001 and No. 58-1950-4-401. Any opinions, findings, conclusions or recommendations expressed in this publication are those of the authors, and do not necessarily reflect the view of the U.S. Department of Agriculture. An erratum to this article is available at .     

Light and hens as attraction factors of Nyssomyia whitmani in a rural area, Southern Brazil

OBJECTIVE: To verify the influence of traps with electric light and hens as factors that attract sandflies and compare results between capture methods. METHODS: The study was conducted in the Palmital Farm, Southern Brazil. Sandfly collections were conducted with Falc?o traps and an electric aspirator, fortnightly, between 8 p.m. and 11 p.m. in the presence or absence of light and hens in peridomiciliary areas, from September 1998 to June 1999. RESULTS: A total of 43,767 specimens from eight species of sandflies were collected: Nyssomyia whitmani, N. neivai and Migonemyia migonei constituting 99.9% of the total collected, with predominance of N. whitmani. The number of this species collected inside the hen's shed in the presence of hens (21,045) was greater than in their absence (10,434). In the presence of hens, with distinct intensities of light, a larger number of N. whitmani samples were collected with 3W light. In the presence of hens and light (3W), the number of N. whitmani collected with the electric aspirator (5,141) was superior to that collected with the Falc?o trap (1,675). In the absence of light, with or without the presence hens, there was no difference between the numbers of N. whitmani collected with the electric aspirator or the Falc?o trap. CONCLUSIONS: Hens and electric light together attract more N. whitmani to peridomicilary areas. The number of N. whitmani collected with an electric aspirator inside a hen's shed with the presence of hens and light is greater than those collected with a Falc?o trap in the same conditions.     

Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia

In children with acute lymphoblastic leukemia (ALL), response to treatment is assessed by bone marrow aspiration. We investigated whether minimal residual disease (MRD) can be effectively monitored in peripheral blood. We used flow cytometric techniques capable of detecting 1 leukemic cell among 10 000 or more normal cells to compare MRD measurements in 718 pairs of bone marrow and peripheral blood samples collected from 226 children during treatment for newly diagnosed ALL. MRD was detected in marrow and blood in 72 pairs and in marrow but not in blood in 67 pairs; it was undetectable in the remaining 579 pairs. Remarkably, findings in marrow and blood were completely concordant in the 150 paired samples from patients with T-lineage ALL: for each of the 35 positive marrow samples, the corresponding blood sample was positive. In B-lineage ALL, however, only 37 of 104 positive marrow samples had a corresponding positive blood sample. Notably, peripheral blood MRD in these patients was associated with a very high risk for disease recurrence. The 4-year cumulative incidence of relapse in patients with B-lineage ALL was 80.0% +/- 24.9% for those who had peripheral blood MRD at the end of remission induction therapy but only 13.3% +/- 9.1% for those with MRD confined to the marrow (P =.007). These results indicate that peripheral blood may be used to monitor MRD in patients with T-lineage ALL and that peripheral blood MRD may provide strong prognostic information in patients with B-lineage ALL.