Bundle branch block patterns, age, renal dysfunction, and heart failure mortality

BACKGROUND: The determinants of bundle block patterns and their relationship to mortality in heart failure patients is not completely understood. METHODS: We evaluated 2907 consecutive patients admitted to an intensive care unit with decompensated heart failure over 8 years. Clinical and echocardiographic factors were analyzed using multivariate techniques. All-cause mortality was available on greater than 99.0% of patients at a median of 23 months after discharge. RESULTS: Right and left bundle branch blocks occurred in 211 (7.3%) and 386 (13.2%), p<0.0001. Older age, decreased left ventricular ejection fraction, and renal dysfunction were all found to be independently associated with bundle branch block patterns. Mortality rates for the subgroups of QRS<120 ms, right bundle branch block and left bundle branch block, over a mean follow-up of 23.4+/-2.6 months were 46.1%, 56.8% and 57.7%, p<0.0001 for comparison of QRS<120 ms versus either bundle pattern. Cox proportional hazards model adjusting for age, sex, ejection fraction, and renal function demonstrated graded decrements in survival in those with QRS<120 ms, right bundle branch block and left bundle branch block, p=0.03. CONCLUSIONS: In patients hospitalized with severe heart failure, age, left ventricular dysfunction, and renal dysfunction are associated with bundle branch block patterns. When controlling for these factors, bundle branch block patterns are independently associated with slightly higher all cause mortality after discharge.     

Cognitive and motor function of neurologically impaired extremely low birth weight children

BACKGROUND:

Rates of neurological impairment among extremely low birth weight children (ELBW [<1 kg]) have decreased since 2000; however, their functioning is unexamined.

OBJECTIVE:

To compare motor and cognitive functioning of ELBW children with neurological impairment, including cerebral palsy and severe hypotonia/hypertonia, between two periods: 1990 to 1999 (n=83) and 2000 to 2005 (n=34).

METHODS:

Measures of function at 20 months corrected age included the Mental and Psychomotor Developmental Indexes of the Bayley Scales of Infant Development and the Gross Motor Functional Classification System as primary outcomes and individual motor function items as secondary outcomes.

RESULTS:

Analysis failed to reveal significant differences for the primary outcomes, although during 2000 to 2005, sitting significantly improved in children with neurological impairment (P=0.003).

CONCLUSION:

Decreases in rates of neurological impairment among ELBW children have been accompanied by a suggestion of improved motor function, although cognitive function has not changed.     

Calcium phosphate coprecipitation greatly enhances transduction of cardiac myocytes and vascular smooth muscle cells by lentivirus vectors

BACKGROUND: Lentivirus vectors provide a delivery system that can both transduce nondividing cells and integrate transgenes into the genome of target cells without cytotoxicity. However, their relatively low transduction efficiency presents a significant obstacle to progress. OBJECTIVES: In the present paper, a simple and easy method using calcium phosphate (CaPi) to enhance the efficiency of lentivirus gene transfer in both vascular smooth muscle cells and cardiac myocytes is reported. METHODS AND RESULTS: Delivery of lentivirus vectors in the presence of CaPi coprecipitates increased vector-encoded transgene expression up to 13-fold. Of interest, the magnitudes of enhancement of transgene expression by CaPi coprecipitates in 293T cells, vascular smooth muscle cells and cardiac myocytes were greater during brief periods (10 min and 120 min) of virus-cell contact than during long periods (16 h). Moreover, with a short duration of incubation with CaPi coprecipitates (up to 120 min), there was little evidence of direct cell toxicity. CaPi coprecipitates had no effect on host range specificity of ecotropic viruses and thus appears to enhance transduction efficiency physiologically by facilitating physical interaction between virus and cell. CONCLUSIONS: These data show that lentivirus with CaPi coprecipitates increases both the efficiency and the speed of gene transfer. These approaches provide an efficient method and an improved tool for research and possibly for therapy of cardiovascular diseases.     

Phospholipids and sialic acid changes produced by vitamin D3 on intestinal mitochondria

Vitamin D3 administration to vitamin D-deficient chicks produces, 24 hours after treatment, a large increment of phospholipids in mitochondria from intestinal mucosa. Proportion of the different phospholipid classes and fatty acid composition of the organelles were not modified by that treatment. A time course study of the effects of 1,25(OH)2D3 on calcium absorption and sialic acid content of intestinal mitochondria glycoproteins showed that both effects were correlated. The results suggest that either vitamin D or the increase of calcium transfer are involved in the make up of intestinal mitochondria membranes.     

Subcellular trafficking of HPMA copolymer-Tat conjugates in human ovarian carcinoma cells.

One of the main obstacles to efficient intracellular delivery of therapeutic macromolecules is the barrier posed by the plasma membrane. In this study, the cell penetrating peptide Tat was conjugated to a synthetic macromolecule based on N-(2-hydroxypropyl)methacrylamide (HPMA) and its subcellular distribution in human ovarian carcinoma cell lines was studied. The Tat peptide mediated uptake resulted in cytoplasmic and nuclear localization and was found to be energy independent. Time and concentration studies verified the rapidity and dependence of the transport process on these parameters. Enhanced uptake of a polymer bound anticancer drug doxorubicin was also demonstrated. These results were corroborated independently by subcellular fractionation.     

Comparative analysis of clinical, biochemical and genetic aspects associated with bone mineral density in small for gestational age children

Clinical, biochemical and genetic analysis related to bone mineral density (BMD) were carried out in children born small for gestational age (SGA) that failed to achieve postnatal catch-up growth (CUG), SGA children that completed CUG and adequate for gestational age (AGA) children. Serum IGF-I, IGF-II, IGF binding protein-3 and acid-labile subunit were lower in the SGA-CUG children as compared with the other groups. Frequencies of polymorphic variants of vitamin D receptor, estrogen receptor and collagen genes were similar among groups. The genotype 194-192 of the IGF-I gene was higher in the SGA-CUG and 196-192 was higher in the SGA+CUG group. In the SGA-CUG group, the genotype SS of the COLIA1 gene was associated with lower BMD. Therefore, IGF system and COLIA1 polymorphism distinguish prepubertal SGA-CUG children from the SGA+CUG children of the same age. Furthermore, COLIA1 polymorphism could be useful to predict osteopenia in SGA-CUG children.     

Chemotaxis of Pseudomonas sp. to caffeine and related methylxanthines

Pseudomonas sp. isolated from soil of coffee plantation area has been shown to degrade higher concentrations of caffeine ( approximately 15 g l(-1)) by N-demethylation at a rate higher than what has been reported for any strain so far. This strain exhibits positive chemotaxis towards caffeine (1,3,7-trimethylxanthine) in swarm plate assay and modified capillary assay in a dose dependant manner. Related methylxanthines and xanthine also act as chemoattractants for the strain with the highest relative chemotactic response (RCR) seen for xanthine. Chemotaxis in Pseudomonas sp. is possibly plasmid mediated as indicated by positive chemotaxis of plasmid transformed E. coli DH5alpha. The chemotactic abilities of Pseudomonas sp. combined with higher rates of degradation of caffeine can be used in the development of strategies for biodecaffeination of caffeine containing wastes.     

Genetic Alterations in Thyroid Tumor Progression: Association with p53 Gene Mutations

To identify the genetic events that must be involved in thyroid tumor progression, we initially investigated p53 gene alterations in 10 papillary adenocarcinomas, 4 follicular adenocarcinomas, and 8 undifferentiated carcinomas. Base substitutional mutations in exons 5 to 8 and loss of heterozygosity (LOH) of the p53 gene were not detected in papillary or follicular adenocarcinomas. However, 7 of 8 undifferentiated carcinomas were carrying base substitutional mutations, and LOH was detected in 3 of 5 informative cases. Furthermore, to verify that the p53 gene alterations are truly involved in tumor progression, DNA from individual foci of the four undifferentiated carcinomas coexisting with a differentiated focus and from one follicular adenocarcinoma with an undifferentiated focus was analyzed by direct sequencing and polymerase-chain-reaction-restriction-fragment-length polymorphism (PCR-RFLP). Base substitutional mutations in the p53 gene from exons 5 to 8 were identified exclusively in the undifferentiated foci, but not in the differentiated foci. LOH was observed in 3 of 4 informative undifferentiated foci. In one of these positive cases, LOH was observed in both papillary adenocarcinoma and undifferentiated carcinoma. However, a p53 gene mutation at codon 248 was detected in the undifferentiated carcinoma but not in the papillary adenocarcinoma. The results imply that LOH occurs first in papillary adenocarcinoma followed by a p53 mutation during the transition from papillary adenocarcinoma to undifferentiated carcinoma. Maintenance of LOH during tumor progression excludes the possibility that these different histological foci are derived from different origins and represents molecular evidence that undifferentiated carcinoma is very likely derived from preexisting papillary adenocarcinoma. Furthermore, these results strongly suggest that the mutated p53 gene plays a crucial role in de-differentiation during the progression of thyroid tumors.     

Role of brachytherapy in the management of desmoid tumors

From 1977 to 1982, fourteen patients with desmoid tumors underwent surgery and brachytherapy. Surgery ranged from biopsy to complete or partial excision of the tumor. Most of these patients had locally advanced tumor or positive margins. A high recurrence rate is expected in such a group if treated by surgery alone. In twelve out of fourteen patients the treatment was considered curative when all disease sites could be encompassed. In the remaining two patients the treatment was considered palliative because the tumor encroaching on to the spinal cord was left untreated. Ten out of twelve curatively treated patients have remained free of recurrence at a minimum of 2 year follow-up. Five of them were followed from 4-6 years. In the palliatively treated group, one patient is alive with active disease at 18 months. Three patients developed complications with wound healing. This experience suggests that surgery and brachytherapy treatment for desmoid tumor results in higher local control than expected from surgery alone in this selected group of patients.