Acute kidney injury during colistin therapy: a prospective study in patients with extensively-drug resistant Acinetobacter baumannii infections.

The study aimed to prospectively assess incidence and risk factors for colistin-associated nephrotoxicity. This is a secondary analysis of a multicentre, randomized clinical trial, comparing efficacy and safety of colistin versus the combination of colistin plus rifampicin in severe infections due to extensively drug-resistant (XDR) Acinetobacter baumannii. The primary end point was acute kidney injury (AKI) during colistin treatment, assessed using the AKI Network Criteria, and considering death as a competing risk. A total of 166 adult patients without baseline kidney disease on renal replacement therapy were studied. All had life-threatening infections due to colistin-susceptible XDR A. baumannii. Patients received colistin intravenously at the same initial dose (2 million international units (MIU) every 8 h) with predefined dose adjustments according to the actual renal function. Serum creatinine was measured at baseline and at days 4, 7, 11, 14 and 21 (or last day of therapy when discontinued earlier). Outcomes assessed were 'time to any kidney injury' (AKI stages 1-3) and 'time to severe kidney injury' (considering only AKI stages 2-3 as events). When evaluating overall mortality, AKI occurrence was modelled as a time-dependent variable. AKI was observed in 84 patients (50.6%, stage 1 in 40.4%), with an incidence rate of 5/100 person-days (95% CI 4-6.2). Risk estimates of AKI at 7 and 14 days were 30.6% and 58.8%. Age and previous chronic kidney disease were significantly associated with any AKI in multivariable analysis. Neither 'any' nor 'severe AKI' were associated with on-treatment mortality (p 0.32 and p 0.54, respectively). AKI occurs in one-third to one-half of colistin-treated patients and is more likely in elderly patients and in patients with kidney disease. As no impact of colistin-associated AKI on mortality was found, this adverse event should not represent a reason for withholding colistin therapy, whenever indicated.

Role of immediate-release morphine (MIR) in the treatment of predictable pain in radiotherapy.

Radiotherapy is crucial in the management of cancer patients in both the curative and palliative settings. However, patients often report pain both during positioning for, and execution of, radiotherapy and this may be a reason for interrupting the radiotherapy session. This observation is common even if the patient is undergoing baseline drug therapy for cancer pain. Recent data suggest that orally administrated immediate-release morphine (MIR) is able to reduce pain in patients with predictable pain. The authors tested a rescue dose of MIR 10 or 20 mg, 20 to 60 minutes before radiotherapy, to verify the effectiveness of MIR in this setting and also to assess the patient's ability to receive the full course of radiotherapy. One hundred forty consecutive patients were evaluated during radiotherapy treatment and visual analogue scale (VAS) and positioning VAS scores were assessed. All patients completed the course of scheduled radiotherapy and pain was well controlled, despite the fact that previous pharmacological treatment had not been able to completely control chronic cancer pain. These data strongly suggest a role for MIR pretreatment in patients with pain due to positioning during radiotherapy.

Recent Developments in IMRT: Therascan, a new Prototype of Linear Accelerator dedicated to Intensity Modulated Radiotherapy

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Estimation of parameters of allometric equations.

Accurate parameter estimation of allometric equations is a question of considerable interest. Various techniques that address this problem exist. In this paper it is assumed that the measured values are normally distributed and a maximum likelihood estimation approach is used. The computations involved in this procedure are reducible to relatively simple forms, and an efficient numerical algorithm is used. A listing of the computer program is included as an appendix.

Sanfilippo B syndrome (MPS III B): altered residual alpha-N-acetylglucosaminidase activity in an unusual sibship.

We studied the residual alpha-N-acetylglucosaminidase activity in two siblings with severe and mild Sanfilippo B syndrome. No striking differences were demonstrated between the mutant enzymes from the severe and the mild case. However we found an altered enzyme activity characterized by displacement of the pH optimum towards basic values compared to the pH optimum of the normal enzyme, higher stability to heat and to Hg2+ ion treatment. It is suggested that the Sanfilippo B disease in this sibship is due to a mutation of a structural gene coding for alpha-N-acetylglucosaminidase.

Sanfilippo B syndrome (MPS III B): mild and severe forms within the same sibship.

Clinical heterogeneity for Sanfilippo B syndrome (MPS III B) in the same family has never been reported previously. We describe two clinically severe cases and one clinically mild case of MPS III B in a Neapolitan sibship. We could not detect N-acetyl-alpha-D-glucosaminidase activity in the sera of either the severe or mild cases. Mucopolysacchariduria mainly due to heparan sulfate excretion was consistently high in the severely affected patients and extremely variable in the mildly affected one.

[Preparation of iduronate sulfatase from the human placenta]. / Preparazione di iduronato solfatasi da placenta umana.

The preparation of the enzyme iduronate sulfatase from human placenta has been undertaken. The substrate O-(alpha-L-idopyranosyluronic acid 2-sulfate) (1 leads to 4)-2,5-anhydro-D-[3H]mannitol 6-sulfate was used to measure the enzymatic activity. The enzyme shows a pH optimum of 4.0 in 0.1 M sodium formiate or acetate buffer. Chromatography on DE-52 gives a 5.4 fold purification. The enzyme is inhibited by NaCl or KCl: in 20 mM salt the reaction rate was only 63% and 34% respectively. Inhibition by salt can be removed by extensive dialysis after the chromatographic step.