Pure red cell aplasia associated with large granular lymphocytic leukemia: a rare association in Western countries

The coexistence of large granular lymphocytic leukemia (LGLL) and pure red cell aplasia (PRCA) has been previously described, but is rare in Western countries (7% in a recent series of LGLL cases). We present the clinical features, hematological parameters and immunophenotype of two patients with PRCA associated with CD3+ LGLL.     

Molecular motion and orientation distributions in melt-processed, fully aromatic liquid crystalline polyesters from 1H NMR

Fully-aromatic thermotropic liquid crystalline polymers (LCP) containing 4-hydroxybenzoic acid (HBA) and 6-hydroxy-2-naphthoic acid (HNA) were studied with 1H NMR. A two- or three-parameter nematic director distribution in molten or nearly molten samples was obtained via rigorous simulation of wideline spectral lineshapes. This methodology was further employed to yield the chain director distribution in macroscopic sections derived from a frozen contraction flow. In addition, the dynamic conformation of polymer chains through the melting transition was monitored via lineshape analysis of samples having (bulk) isotropic director distributions. Extension of rigorous 1H NMR spectral deconvolution to recently developed solid-state NMR imaging sequences is discussed.     

Application of a mechanistic model of bovine milk protein synthesis to examine the use of isotope labeling methods

Two types of models of bovine milk protein synthesis were used to simulate collection and analysis of data from infusion experiments involving isotope-labeled amino acids (AA). Analytical solutions to a system of ordinary differential equations that describe isotope enrichment curves of each AA pool within the mammary gland were derived and are presented. Numerical solutions from a dynamic mechanistic model suggest that normal experimental procedures can affect the shape of enrichment curves and, therefore, results derived from them. Simulation results suggest that standard methods utilizing in vivo isotope kinetics may be of limited value to characterize the metabolism of the bovine mammary gland, especially AA metabolism and milk protein synthesis and secretion. The results clearly demonstrate the flexibility of such models for the testing of many hypotheses and possible experimental protocols.     

Immunization of Aotus monkeys with recombinant Plasmodium falciparum hybrid proteins does not reproducibly result in protection from malaria infection

Plasmodium falciparum antigens SERP, HRPII, MSAI, and 41-3 have shown promise as vaccine components. This study aimed at reproducing and extending previous results using three hybrid molecules. Antibody responses were reproduced in Aotus monkeys, but solid protection from a P. falciparum blood-stage challenge that showed an unintendedly enhanced pathogenicity was not observed.     

A phase I study of adenovirus-mediated wild-type p53 gene transfer in patients with advanced non-small cell lung cancer

Mutations of the tumor suppressor gene p53 are the most common genetic alterations observed in human cancer. Loss of wild-type p53 function impairs cell cycle arrest as well as repair mechanisms involved in response to DNA damage. Further, apoptotic pathways as induced by radio- or chemotherapy are also abrogated. Gene transfer of wild-type p53 was shown to reverse these deficiencies and to induce apoptosis in vitro and in preclinical in vivo tumor models. A phase I dose escalation study of a single intratumoral injection of a replication-defective adenoviral expression vector encoding wild-type p53 was carried out in patients with incurable non-small cell lung cancer. All patients enrolled had p53 protein overexpression as a marker of mutant p53 status in pretreatment tumor biopsies. Treatment was performed either by bronchoscopic intratumoral injection or by CT-guided percutaneous intratumoral injection of the vector solution. Fifteen patients were enrolled in two centers, and were treated at four different dose levels ranging from 10(7) to 10(10) PFU (7.5 x 10(9) to 7.5 x 10(12) particles). No clinically significant toxicity was observed. Successful transfer of wild-type p53 was achieved only with higher vector doses. Vector-specific wild-type p53 RNA sequences could be demonstrated in posttreatment biopsies of six patients. Transient local disease control by a single intratumoral injection of the vector solution was observed in four of those six successfully transduced patients. There was no evidence of clinical responses at untreated tumor sites. Wild-type p53 gene therapy by intratumoral injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective in patients with advanced non-small cell lung cancer.     

Compliance with hypertension treatment: 10 years of publications in Spain

INTRODUCTION: Ten years of publications (1984-1993) about drug compliance in spanish hypertensive patients are presented. MATERIAL AND METHODS: A bibliography search of Medline (EBSCO CD-ROM ver 104.1, act Jul 1995), Indice Médico Espa?ol (CSIC CD-ROM, act Oct 1993) and other sources has been made. RESULTS: 39 articles have been located and 23 investigational publications have been analysed. All the publications, but one, have evaluated the compliance by an indirect method, mainly patient selfdeclaration. The degree of patient compliance determined by interviews, questionnaires or inquiries is 55.5% (IC 95%: 52.7-58.3). The patient compliance in the publications that use methods based in pill counts is 46.4% (IC 95%: 41.6-51.2). The treatment dropout is present in the 18.5% of the patients (IC 95%: 20.5-16.5). CONCLUSIONS: The drug compliance degree in Spanish patients with hypertension is low.