Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593.

PURPOSE: Patients with primary cutaneous melanoma > or = 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival. PATIENTS AND METHODS: A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia. Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness > or = 3 mm. RESULTS: Median follow-up duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND). The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%. There was no benefit from ILP in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP. CONCLUSION: Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.

Comparison of antibiotic drops placed in the conjunctival cul-de-sac to antibiotic ointment applied to the lid margin in reduction of bacterial colonization on the lid margin.

PURPOSE: To compare the efficacy of antibiotic drops placed in the conjunctival cul-de-sac to antibiotic ointment applied to the lid margin in reduction of bacterial colonization on the lid margin. METHODS: A randomized, prospective, single-masked study was conducted on 19 patients with culture-proven colonization of bacteria on the lid margins. Ophthalmic eligibility criteria included the presence of > or =50 colony-forming units/mL (CFU/mL) of bacteria on both right and left lids. Each patient received one drop of ofloxacin in one eye every night for one week, followed by one drop once a week for one month. In the same manner, each patient received bacitracin ointment (erythromycin or gentamicin ointment if lid margin bacteria were resistant to bacitracin) to the lid margin of the fellow eye. Quantitative lid cultures were taken at initial visit, one week, one month, and two months. Fifteen volunteers (30 lids) served as controls. Lid cultures were taken at initial visit, one week, and one month. RESULTS: Both antibiotic drop and ointment reduced average bacterial CFU/mL at one week and one month. Average bacterial CFU/mL reestablished to baseline values at two months. There was no statistically significant difference between antibiotic drop and ointment in reducing bacterial colonization on the lid margin. CONCLUSION: Antibiotic drops placed in the conjunctival cul-de-sac appear to be as effective as ointment applied to the lid margins in reducing bacterial colonization in patients with > or =50 CFU/mL of bacteria on the lid margins.

Effect of chronic hypoglycaemia on glucose concentration and glycogen content in rat brain: A localized 13C NMR study.

While chronic hypoglycaemia has been reported to increase unidirectional glucose transport across the blood-brain barrier (BBB) and to increase GLUT1 expression at the endothelium, the effect on steady-state brain d-glucose and brain glycogen content is currently unknown. Brain glucose and glycogen concentrations were directly measured in vivo using localized 13C magnetic resonance spectroscopy (MRS) following 12-14 days of hypoglycaemia. Brain glucose content was significantly increased by 48%, which is consistent with an increase in the maximal glucose transport rate, Tmax, by 58% compared with the sham-treated animals. The localized 13C NMR measurements of brain glucose were directly validated by comparison with biochemically determined brain glucose content after rapid focused microwave fixation (1.4 s at 4 kW). Both in vivo MRS and biochemical measurements implied that brain glycogen content was not affected by chronic hypoglycaemia, consistent with brain glucose being a major factor controlling brain glycogen content. We conclude that the increased glucose transporter expression in chronic hypoglycaemia leads to increased brain glucose content at a given level of glycaemia. Such increased brain glucose concentrations can result in a lowered glycaemic threshold of counter-regulation observed in chronic hypoglycaemia.

Localized fibrous tumours of the pleura: 15 new cases and review of the literature.

OBJECTIVE: To present a series of localized fibrous tumours of the pleura (LFTP), to define the clinical and histopathological diagnostic criteria of this tumour, and to determine the optimal treatment and follow-up. METHODS: Review of the charts of the patients with the diagnosis of LFTP (formerly called benign fibrous mesothelioma), as well as of all the histological sections, including immunohistochemical stains. Review of the literature with special emphasis on the clinical and histological criteria of malignancy. RESULTS: During the last 30 years, we found 15 patients with a complete clinical chart and histological material, particularly paraffin blocks of the tumour. The mean age was 57 years (range 27-79). Eight patients were asymptomatic, and the remaining seven presented with non-specific symptoms. All but one had complete resection of the tumour, including partial lung resection in two and partial chest wall resection in three. The diagnosis was confirmed by histological review in 15 cases. Immunohistochemical stainings showed positivity for vimentin in all cases, for CD 34 in 80%, but were consistently negative for cytokeratins. Nine tumours were histologically classified as malignant. Among them, five recurred, two of which were responsible for death. One benign tumour recurred after 1 year, and was treated successfully by repeat resection and radiotherapy. Overall, 13 patients (86%) were alive with no evidence of disease between 10 months and 27 years after the first resection. CONCLUSIONS: LFTP is a rare tumour which has a benign clinical course in over 80% of the cases, and is asymptomatic in half the patients. The diagnosis is difficult to establish before operation. Treatment consists of complete resection including adjacent structures if necessary. The clinical behaviour of LFTP cannot be predicted on the basis of histological aspects only. If histologically malignant tumours are more prone to recurrence and poor outcome, broad-based and locally invasive tumours bear a higher risk of recurrence. Long term follow-up is therefore mandatory in all cases in order to perform early re-resection when recurrence occurs.

Acvbp Versus Acvbp Plus Rituximab For Young Patients With Localized Low-Risk Diffuse Large B-Cell Lymphoma: A Study By The Groupe D'etude Des Lymphomes De L'adulte

Introduction: In a prior study, we demonstrated that ACVBP + consolidation was superior to 3 cycles of CHOP + radiotherapy in young patients (pts) with localized aggressive lymphoma (Reyes F et al. N Engl J Med 2005;352:1197). This randomized trial compared in these pts ACVBP vs. ACVBP + a short course of rituximab (R-ACVBP).Methods: untreated pts between 18 and 65y with stage I/II DLBCL and no adverse prognostic factors according to the aa-IPI were eligible. ACVBP consisted of 3 induction cycles given every 2 weeks: doxorubicin (75 mg/m2) day 1, cyclophosphamide (1.2g/m2) day 1, vindesine (2 mg/m2) day 1 and 5, bleomycin (10 mg) day 1 and 5, prednisone (60 mg/m2) day 1 to 5 followed by consolidation with metothrexate, ifosfamide, VP-16 and cytarabine. R-ACVBP consisted of the same regimen combined with 4 doses of rituximab (375 mg/m2) on day 1, 15, 29 and 43. Primary objective was EFS.Results: From 01/04 to 03/08, 223 pts were randomized, 113 in ACVBP and 110 in R-ACVBP arm. Characteristics were: median age 49y (18-65), stage I 63%, extranodal involvement 45%, bulky disease 4%. CR was 94% in ACVBP and 97% in ACVBP arm (ns). With a median follow-up of 43 months, the 3-y EFS was 82% (95% CI, 73% to 88%) in ACVBP and 93% (95% CI, 87% to 97%) in R-ACVBP group (P=0.0487). The 3-y PFS was 83% (95% CI, 74% to 89%) and 95% (95% CI, 89% to 98%) respectively (P=0.0205). OS did not significantly differ with a 3-y estimates of 97% (95% CI, 90% to 99%) for ACVBP and 98% (95% CI, 92% to 100%) for R-ACVBP (P=0.686). In multivariate analysis, a longer PFS was associated with R-ACVBP arm (P=0.0302) and lower b2-m level (P=0.0164). The same proportion of pts (27%) experienced at least 1 SAE in both groups. There were 4 deaths in each arm, with 1 treatment-related death in R-ACVBP (pneumocystis jiroveci pneumonia).Conclusion: the addition of only 4 doses of rituximab to ACVBP significantly improves EFS and PFS in younger pts with low-risk localized DLBCL.

Avaliacao dos resultados cirurgicos com a tecnica da resseccao do musculo de Muller-conjuntiva no tratamento da blefaroptose. [Evaluation of the surgery results of Muller's muscle-conjunctival resection in the treatment of blepharoptosis]

OBJECTIVE: To evaluate the results of Muller's muscle-conjunctival resection for correction of blepharoptosis and to discuss the advantages of this procedure. METHODS: 38 patients (39 eyelids) were submitted to Muller's muscle-conjunctival resection. Blepharoptosis varied from 1.0 mm to 3.0 mm (mean: 2.0 mm). The amount of eyelid elevation produced by phenylephrine guided the amount of tissue to be resected. RESULT: 33 eyelids (85%) treated with this procedure were cosmetically acceptable. CONCLUSIONS: Muller's muscle-conjunctival resection procedure is a relatively simple technique for blepharoptosis, with good levator function and positive 10% phenylephrine test. The advantages are: preservation of tarsus and predictable results.

Amyloïdose cardiaque: une urgence diagnostique [Echocardiographic analysis in cardiac amyloidosis]

Systemic amyloidosis with cardiac involvement may clinically be suspected in the presence of heart failure or arrhythmia of unknown origin. Herein two cases of cardiac amyloidosis are described with a clinical presentation of heart failure refractory to usual treatment. The key role of echocardiography in the diagnosis and prognosis evaluation of cardiac amyloidosis is discussed. A treatment targeted against the generation of amyloid fibril should ideally be initiated before apparition of heart failure.

Localized in vivo hyperpolarization transfer sequences.

In vivo localized and fully adiabatic homonuclear and heteronuclear polarization transfer experiments were designed and performed in the rat brain at 9.4 T after infusion of hyperpolarized sodium [1,2-(13)C(2)] and sodium [1-(13)C] acetate. The method presented herein leads to highly enhanced in vivo detection of short-T(1) (13)C as well as attached protons. This indirect detection scheme allows for probing additional molecular sites in hyperpolarized substrates and their metabolites and can thus lead to improved spectral resolution such as in the case of (13)C-acetate metabolism.

Synovial fluid examination for the diagnosis of synovial amyloidosis in patients with chronic renal failure undergoing haemodialysis

The diagnosis of synovial amyloidosis is based upon synovial biopsy. Synovial fluid (SF) in seven patients with amyloid arthropathy associated with chronic renal failure undergoing haemodialysis were studied. The SF and synovial samples of 10 consecutive patients with seronegative mono- or oligoarthritis served as controls. Six of the seven patients with amyloid positive synovial biopsy specimens showed amyloid in their SF. No amyloid was found in the synovial tissue or fluid of the 10 patients in the control group, the sensitivity being 87.7%. The finding of amyloid in SF was highly reproducible, showing its presence in the same joint on several occasions. The deposits were Congophilia resistant to potassium permanganate pretreatment, and the immunohistochemical analysis proved that they contained beta 2 microglobulin. The high sensitivity and good reproducibility of the method shows that the finding of amyloid in SF is sufficient for the diagnosis of synovial amyloidosis. It is possible to perform immunohis

Hereditary hepatic and systemic amyloidosis caused by a new deletion/insertion mutation in the apolipoprotein AI gene.

We report a Spanish family with autosomal-dominant non-neuropathic hereditary amyloidosis with a unique hepatic presentation and death from liver failure, usually by the sixth decade. The disease is caused by a previously unreported deletion/insertion mutation in exon 4 of the apolipoprotein AI (apoAI) gene encoding loss of residues 60-71 of normal mature apoAI and insertion at that position of two new residues, ValThr. Affected individuals are heterozygous for this mutation and have both normal apoAI and variant molecules bearing one extra positive charge, as predicted from the DNA sequence. The amyloid fibrils are composed exclusively of NH2-terminal fragments of the variant, ending mainly at positions corresponding to residues 83 and 92 in the mature wild-type sequence. Amyloid fibrils derived from the other three known amyloidogenic apoAI variants are also composed of similar NH2-terminal fragments. All known amyloidogenic apoAI variants carry one extra positive charge in this region, suggesting that it may be responsible for their enhanced amyloidogenicity. In addition to causing a new phenotype, this is the first deletion mutation to be described in association with hereditary amyloidosis and it significantly extends the value of the apoAI model for investigation of molecular mechanisms of amyloid fibrillogenesis.