Towards the development of a pediatric ventricular assist device

The very limited options available to treat ventricular failure in children with congenital and acquired heart diseases have motivated the development of a pediatric ventricular assist device at the University of Pittsburgh (UoP) and University of Pittsburgh Medical Center (UPMC). Our effort involves a consortium consisting of UoP, Children's Hospital of Pittsburgh (CHP), Carnegie Mellon University, World Heart Corporation, and LaunchPoint Technologies, Inc. The overall aim of our program is to develop a highly reliable, biocompatible ventricular assist device (VAD) for chronic support (6 months) of the unique and high-risk population of children between 3 and 15 kg (patients from birth to 2 years of age). The innovative pediatric ventricular assist device we are developing is based on a miniature mixed flow turbodynamic pump featuring magnetic levitation, to assure minimal blood trauma and risk of thrombosis. This review article discusses the limitations of current pediatric cardiac assist treatment options and the work to date by our consortium toward the development of a pediatric VAD.     

The postnatal development of glial fibrillary acidic protein and neurofilament triplet proteins in rat brain stem

Cytoskeletal preparations containing both the glial fibrillary acidic protein and the neurofilament triplet proteins were prepared from brain stems of rats at different ages and the individual peptides separated in polyacrylamide gels. Stained peptide bands were quantitated as the area under peaks generated by densitometric scanning. Peak areas were converted to grams of protein based on total gel dye binding and total protein applied to the gels. Between 5 and 30 days, the concentration of the peptide (g of peptide/mg of tissue protein) of apparent molecular weight 51,000 (corresponding to the glial fibrillary acidic protein), increased 3 fold. The corresponding increase in total concentration of the three peptides corresponding to the neurofilament proteins was 4.5 fold. However, the increase in concentration of the individual neurofilament peptides was each different. Very little of the apparent molecular weight 210,000 neurofilament peptide was present at 5 days and its concentration increased 11 fold by 30 days compared to about 3.5 fold for the other two neurofilament peptides. These results are in general agreement with studies using immunological techniques and the methods have the advantages of using readily available techniques and allowing the simultaneous comparison of both neuronal and glial specific filaments during development.     

Appearance of myelin proteins in rat sciatic nerve during development.

Rats between 5 and 45 days of age were sacrificed and their sciatic nerves dissected. Myelin was prepared from these sciatic nerves by a procedure involving purification on discontinuous sucrose gradients. The proteins of whole sciatic nerves at different ages and the proteins derived from the myelin isolated from these sciatic nerves were examined by discontinuous polyacrylamide gel electrophoresis in buffers containing sodium dodecyl sulfate. Over half of the proteins of sciatic nerve myelin migrated in a single band on the gel (P0). There were only minor changes in the protein distribution of sciatic nerve mylein during development. In contrast, the polyacrylamide gel patterns of whole sciatic nerve homogenate changed markedly during development between 5 and 15 days of age. The amount of P0 protein as a proportion of the total sciatic nerve protein increased from 3% at 5 days of age to 13% at 15 days of age after which it remained constant. Several other proteins which were also characteristic of the isolated myelin increased in relative importance during this time period. Parallel experiments dealing with a metabolic parameter of myelinogenesis, incorporation of intraperitoneally injected [35S]sulfate into sulfatide, were conducted. The maximum synthesis of sulfatide occurred between 6 and 16 days of age, coincident with the marked accumulation of myelin proteins in sciatic nerve.     

Predictors of pleural malignancy in patients with pleural effusion undergoing thoracoscopy

STUDY OBJECTIVES: Thoracoscopic pleural biopsy is highly accurate in the diagnosis of pleural malignancy. However, no scientific evidence is currently available to guide the physician's decision as to when and in which patients with pleural effusion thoracoscopy is indicated. The application of predictive criteria of malignancy might improve the indication of thoracoscopy in patients with undiagnosed pleural effusion. METHODS: Prospective study of 93 patients referred for thoracoscopy at a tertiary hospital. Clinical variables were obtained prior to thoracoscopy by clinical history and review of previous data, patient interview, and physical examination. Radiologic variables were obtained by evaluation of chest radiograph and chest CT images by two independent readers. After thoracoscopy, all patients without a diagnosis were sent for long-term follow-up. RESULTS: Thoracoscopy demonstrated 94% sensitivity and 100% specificity in the diagnosis of pleural malignancy. Variables, which in a multivariate model are associated with pleural malignancy, include a symptomatic period > 1 month, absence of fever, blood-tinged pleural fluid, and chest CT scan findings suggestive of malignancy. Receiver operating characteristic analysis showed that the use of these four criteria offered adequate classification in 95% of patients. Twenty-eight patients had all four criteria, and all had malignancy; 21 patients had at most one criterion, and none had malignancy. CONCLUSION: Clinical and radiologic criteria of patients with pleural effusion permit different risk levels for pleural malignancy to be distinguished. Consequently, application of the four proposed criteria permits better indication of thoracoscopy in patients with undiagnosed pleural effusion.     

Launch and preliminary analysis of Hospital de La Princesa's inter-specialists biological therapies unit

We herein describe an inter-specialists unit for the monitoring and management of biological therapies and analyze the utilization of biological agents across specialties and diseases. Protocols and therapeutic objectives, as well as outcomes and protocol deviations, are shared and discussed periodically between specialists. All patients treated at one centre with any biological treatment from January 2000 by rheumatology, gastroenterology, dermatology, or neurology, regardless diagnosis, are identified by Clinical Pharmacy and included in an ongoing database that detects use and outcome. The drugs, survival, and reasons for discontinuation differ significantly across specialties. This approach has helped us recognizing the challenges and size of the problem of sharing expensive medications across specialties, and has served as a starting point to contribute to the better use of these compounds.     

DFNB79: reincarnation of a nonsyndromic deafness locus on chromosome 9q34.3

Genetic analysis of an inbred Pakistani family PKDF280, segregating prelingual severe to profound sensorineural hearing loss, provided evidence for a DFNB locus on human chromosome 9q34.3. Co-segregation of the deafness trait with marker D9SH159 was determined by a two-point linkage analysis (LOD score 9.43 at θ=0). Two additional large families, PKDF517 and PKDF741, co-segregate recessive deafness with markers linked to the same interval. Haplotype analyses of these three families refined the interval to 3.84 Mb defined by D9S1818 (centromeric) and D9SH6 (telomeric). This interval overlaps with the previously reported DFNB33 locus whose chromosomal map position has been recently revised and assigned to a new position on chromosome 10p11.23–q21.1. The nonsyndromic deafness locus on chromosome 9q segregating in family PKDF280 was designated DFNB79. We are currently screening the 113 candidate DFNB79 genes for mutations and have excluded CACNA1B, EDF1, PTGDS, EHMT1, QSOX2, NOTCH1, MIR126 and MIR602.     

PET in abdominal pathology: advantages and limitations

New oncologic procedures are currently more focused on the biological features of tumors. The ideal objective is the administration of personalized effective treatments for each patient that affects not just the location and spread of disease but also special metabolic characteristics of tumoral cells. Radiologic diagnostic methods are extremely important in the management of the patient for staging, restaging, and evaluation of treatment response, and clinicians are avid for some additional functional and metabolic information. Further, they need more dynamic methods for follow-up. Nuclear Medicine and positron emission tomography (PET) in many cases can meet this requirement, although it is not perfect, at least at the present time. Currently 2-(¹⁸F)fluoro-2-desoxi-D-glucose positron emission tomography is being widely used for oncologic purposes. Its information can be very useful in abdominal diseases and must be taken into account with the results of radiologic imaging. Thus, many changes in the choice of treatment are seen. However, it is very important to know that sometimes there is a lack of specificity that has to be considered.