Desferrioxamine therapy accelerates clearance of iron deposits after bone marrow transplantation for thalassaemia

We treated 18 heavily iron-loaded patients who had become ex-thalassaemics after bone marrow transplantation with subcutaneous desferrioxamine therapy for 5-20 months. As determined using serum ferritin concentration, transferrin saturation and stainable liver iron obtained in follow-up biopsies, marked decreases in body iron stores were observed with this regimen. Moreover, the liver function tests demonstrate a trend to normalization in all cases. Local skin reactions to desferrioxamine were the only toxicities observed. We conclude that pharmacological iron chelation is a safe and effective therapy in the reduction of iron deposits in this clinical situation; it therefore represents a valid alternative to phlebotomy in selected patients.     

Preliminary report: BGLIIA-BGLIIB haplotype of growth hormone cluster is associated with glucose intolerance in non-insulin-dependent diabetes mellitus and with growth hormone deficit in growth retardation.

We studied 101 growth-retarded children from the population of Ancona (Italy). Plasma growth hormone (GH) levels at the end of insulin and clonidine tests were considered for classification of children into 3 categories according to severity of GH deficit: total deficit of GH (TD), partial deficit (PD, and familiar short stature (FSS; no deficit of GH). The BGLIIA*2/BGLIIB*1 haplotype of GH cluster that was previously found to be negatively associated with severe glucose intolerance in non-insulin-dependent diabetes mellitus (NIDDM) is negatively associated with GH deficit in growth-retarded children. The hypothesis that intrauterine growth retardation and glucose intolerance in adult life could be phenotypes of the same underlying genotype has been recently put forward. The present observation suggests that genes influencing both growth and glucose tolerance are encoded in the GH cluster.     

Comparison Between 64Cu-PSMA-617 PET/CT and 18F-Choline PET/CT Imaging in Early Diagnosis of Prostate Cancer Biochemical Recurrence

Purpose

To evaluate the diagnostic performance of ⁶⁴Cu-PSMA-617 positron emission tomography (PET) with computed tomography (CT) for restaging prostate cancer after biochemical recurrence (BCR) and to compare it with ¹⁸F-choline PET/CT in a per-patient analysis.

A pharmacy intervention program: recognizing pharmacy's contribution to improving patient care

An on-line pharmacy intervention program developed to document and evaluate pharmacist's contribution to patient care is described. Over a 1-year period, the number and types of interventions and their impact on patient care were collated and reviewed by a clinical coordinator. Two thousand four hundred ninety-nine interventions were recorded. The most common types of interventions were order clarification/change (18%), pharmacokinetic consult (16%), chart review (13%), restricted drug follow-up (8%), discharge medication screen (7%), initiate drug therapy (6%), drug information (5%), discontinued drug (4%), and therapeutic alternative (4%). There were 3459 impact codes assigned to these interventions. Forty-one percent decreased toxicity, 35% increased efficacy, 17% decreased cost, 16% avoided allergy or drug interaction, 8% improved compliance, and 22% were classified as other. Our analysis found that pharmacy interventions elevated the standard of care and prevented major organ damage and potentially life-threatening events. This program shows that pharmacists play a significant role in improving patient outcomes.     

Pubertal development in thalassaemic patients after allogenic bone marrow transplantation

To obtain further insight into gonadal function, a series of 50 prepubertal patients with -thalassaemia major (24 boys and 26 girls) aged from 12.6 to 18 years (mean 15 years) who had received a bone marrow transplantation (BMT) during childhood or the peripubertal period, at the age of 3.6–14.5 years (mean 10.8 years), were periodically re-evaluated at intervals of 6–12 months. The last evaluation was done 1–9 years (mean 4.2 years) after BMT. At each examination we measured height, pubertal stage, plasma gonadotrophins (LH and FSH) before and after the GnRH stimulation test (i.v.), sex steroids (total and free testosterone in males, and 17-oestradiol in females), serum ferritin and bone age. Fourty percent of patients entered or passed through puberty normally despite clinical and hormonal evidence of gonadal dysfunction in most of them. A correlation was not found between the pubertal stage and age at BMT, and no statistical difference between patients who did not enter into puberty and patients with spontaneous pubertal development was found in serum ferritin levels. Our data confirm that gonads in male and female thalassaemic patients are exposed to the cytotoxic effects of the preparative transplant regime with alkylating agents. In some patients absence of pubertal development was due to gonadotrophin insufficiency, probably secondary to previous iron overload. These findings emphasize the need for a vigilant long-term follow up study of thalassaemic patients who have had BMT.Part of this work has been presented at the 2nd International Symposium on Bone Marrow Transplantation in Thalassemia. Pesaro, Italy, 1992 and was supported by A.I.L., Pesaro, Italy.     

Enantiopure polythiophene nanoparticles. Chirality dependence of cellular uptake,intracellular distribution and antimicrobial activity

The use of intrinsic chiral molecules opens the door to bio-imaging specific tools and to the development of target-therapy. In this work the synthesis and characterization of polythiophenes with alkyl side chains containing one R or S chiral carbon is reported. Enantiopure chiral nanoparticles (R or S NPs) were prepared from the polymers by a reprecipitation method. UV-vis, photoluminescence and circular dichroism spectroscopy of the NPs are described. In vitro analysis and metabolic assays show that both R and S NPs are efficiently taken-up by fibroblast cells without signs of toxicity. SDS-PAGE experiments show that formation of hard protein ‘corona’ enhances the chirality difference between nanoparticles. Co-localization experiments demonstrate that the cells are able to discriminate between the enantiomeric R and S nanoparticles. Finally, experiments carried out on Gram negative and Gram positive bacteria show that the enantiomeric NPs display different antibacterial activity.

The use of intrinsic chiral molecules opens the door to bio-imaging specific tools and to the development of target-therapy.     

Uptake and distribution of labeled antibodies into pH-sensitive microgels

We investigated the uptake and release of labeled antibodies from pH-sensitive hydrogel microparticles (i.e. microgels) by means of fluorescence analysis of labeled biological samples. The poly(methacrylic acid) (PMAA) hydrogel is a carbon-based network having carboxylic groups on the surface that dissociate according to their acid–base equilibrium. The ability of the PMAA microgel to encapsulate and release anti-CD4 and anti-CD8 monoclonal antibodies (MAbs), differing for the isotype and labeled with highly photostable fluorophore, was studied in solution by photoluminescence spectroscopy. The experimental results indicated that the uptake and release of the tested antibodies were controlled by pH. Furthermore, confocal microscopy analysis in the solid state revealed that the distribution of the labeled antibodies either on the surface or in the core of the microgel matrix was related to the specific properties of these MAbs.     

Comparison of the measurement of surface or total platelet-associated IgG in the diagnosis of immune thrombocytopenia

Platelet-associated IgG (PAIgG) can be measured on intact platelets or following platelet lysis. Measurement of PAIgG following platelet lysis may provide different or additional information compared to PAIgG measured on intact platelets. The PAIgG of lysed platelets represents "total" PAIgG, ie, IgG on the surface of platelets plus any IgG that was inside the platelet. To investigate the clinical relevance of the two types of PAIgG assay we performed a prospective study on washed platelets collected from 47 patients with idiopathic thrombocytopenic purpura (ITP). The PAIgG was measured on intact and lysed platelets using an immunoradiometric assay. Platelet-associated IgG was 2-3 times higher when measured on lysed platelets from healthy controls or patients with ITP compared to PAIgG measured on the same intact platelets. The higher level of PAIgG observed following platelet lysis was not due to the reactions not achieving equilibrium. Using lysed platelets, PAIgG was elevated on 29 of 47 samples from different ITP patients and elevated in 31 samples when measured on intact platelets. The PAIgG is invariably higher when measured following platelet lysis compared measurements made on intact platelets. Neither technique offers a diagnostic advantage over the other.