Current options in prosthetic vascular graft infection

Debate continues over which procedure is the best treatment for prosthetic graft infections. We retrospectively reviewed the medical records at our institution for all vascular graft infections that occurred from 1985 to 1995 to evaluate their occurrence, treatment, and outcome. Twenty-four patients had prosthetic graft infections. The average patient age was 62 years, and 67 per cent of the patients studied were men. The initial operation was for treatment of occlusive disease in 92 per cent of the patients, and aortofemoral bypasses were the most common procedures performed (15 of 24 patients, 63%). The average interval from graft implantation to presentation of infection was 29 months. In lower-extremity bypasses, the site of infection was most commonly in the groin (87%). Gram-positive organisms, including coagulase-negative Staphylococcus (32%) and Staphylococcus aureus (28%), were the most frequently isolated bacteria. Thirty procedures were performed for management of the graft infections. Extra-anatomic bypass was associated with no recurrent graft infections. Graft preservation was successful in two cases of early S. aureus infection (less than 1 year after original procedure), and in situ graft replacement was successful in all four cases of late-appearing coagulase-negative Staphylococcus infection (more than 1 year after original procedure). Both treatments failed in all five cases of Gram-negative infection (P = 0.008 by Fisher's exact test). The overall mortality and amputation rates were 17 per cent and 21 per cent, respectively, without significant differences between the treatment modalities. Extra-anatomic bypass remains the best treatment for prosthetic graft infection. In situ replacement and graft preservation treatments should be selective and based on presentation of the infection and the type of pathogenic organism.     

The detection of oligonucleotide N3'-->P5' phosphoramidate/RNA duplexes with capillary gel electrophoresis

Oligonucleotide N3'-->P5' phosphoramidates (3'-phosphoramidates) are DNA analogs that are presently under investigation as potential therapeutic agents. These compounds may also hold promise as a diagnostic tool. Here, we describe a rapid method for the analysis of single-stranded RNA fragments utilizing 3'-phosphoramidate oligonucleotides as probes in conjunction with capillary gel electrophoresis (CGE). 3'-Phosphoramidate 9-mers were mixed with complimentary RNA, and CGE was used to monitor duplex formation. Complimentary strands of RNA and 3'-phosphoramidate formed duplexes that gave unique relative mobilities based on an internal standard. The ability of CGE to discriminate between perfect duplexes and duplexes that contain a base mismatch was also investigated. However, the primary focus of this work was to determine CGE's ability to detect the presence of the 3'-phosphoramidates/RNA duplex under routine electrophoretic running conditions. Polyacrylamide gel electrophoresis analysis was utilized to verify duplex formation.     

Diverse Fab specific for acetylcholine receptor epitopes from a myasthenia gravis thymus combinatorial library

The muscle weakness in myasthenia gravis (MG) is caused by heterogeneous high-affinity IgG autoantibodies to the nicotinic acetylcholine receptor (AChR), a complex ion channel glycoprotein. These antibodies are clearly responsible for reducing AChR numbers at the neuromuscular junction in myasthenia; however, the origins, diversity, specificity and pathogenicity of individual antibodies have not yet been established. We have cloned and characterized four different AChR-specific Fab from an MG patient's thymus by screening an IgG1/kappa gene combinatorial lambda phage library with soluble human AChR labeled with [125I] alpha-bungarotoxin. Unlike most previously cloned human antibodies, all four Fab immunoprecipitated soluble human muscle AChR. Two Fab strongly inhibited binding of mAb to the main immunogenic region on the alpha subunits and one Fab bound to an epitope on the fetal-specific gamma subunit. In sensitivity and fine specificity, these Fab resembled the anti-AChR antibodies found in many MG patients, including the donor. The closest germline counterparts for their heavy chains were in VH families 1, 3 and 4; however, there were many differences consistent with an antigen-driven response of diverse B cell clones. The combinatorial approach holds promise for further analysis of human autoantibodies.     

Urine osmolality and conductivity as indices of hydration status in athletes in the heat

PURPOSE: The purpose of this study was to determine a quick and easy method for assessment of day-to-day hydration status in athletes in the heat. METHODS: Measurement of the osmolality of the first urine sample of the day collected after wakening but before breakfast established a standardized collection procedure to allow day-to-day comparisons of individuals. RESULTS: Laboratory measurements established that a difference in osmolality is found when individuals are dehydrated by a moderate extent in comparison with an euhydrated situation: the osmolality of the first morning urine sample of control subjects (N = 11) averaged over 5 d was 675 (+/- 232) mosmol.kg-1 (mean +/- SD). For subjects who were hypohydrated by exercise followed by fluid restriction, morning urine osmolality was 924 (+/- 99) mosmol.kg-1 (P < 0.001, N = 11, averaged over 7 d). Field measurements from 29 athletes undertaking warm weather training indicated that the athletes could, with appropriate feedback, maintain a satisfactory hydration status. Athletes in weight category sports tended to record a higher morning urine osmolality, reflecting their attempts to dehydrate: recorded values were 627 (+/- 186) mosmol.kg-1 (nonweight category sports, N = 8), 775 (+/- 263) mosmol.kg-1 (boxers, N = 15) and 777 (+/- 254) mosmol.kg-1 (wrestlers, N = 6). Results obtained with a hand-held portable conductivity were compared with those from measured osmolality. CONCLUSIONS: The findings suggest that such an instrument could provide athletes with reliable information as to their hydration status from measurement of the first morning urine of the day and therefore provide a quick and easy method for achieving an approximation of hydration status from day-to-day.     

Controlling bacterial contamination of an enteral formula through the use of a unique closed system: contamination, enteral formulas, closed system

Contamination of enteral diets may play an essential role in formula tolerance and safety for patients. Contaminated enteral formula commonly support microbiological growth. Commercially sterile liquid formulas received from the manufacturer are required by the Food & Drug Administration (FDA) to be shelf-stable and free from enteric pathogens. This study examined the use of large volume, closed system containers in a typical nursing home. Large volume (1500 mL) containers with unique pierceable caps and piercing spikes were studied to determine their ability to reduce the incidence of microbiological contamination due to their design and ability to decrease handling requirements. This study took place in a room of a typical nursing home. In this clinical setting, 211 containers and administration spike sets were evaluated following a 36-h hangtime. Contamination was virtually nondetectable. Nursing staff in a clinical facility can effectively utilize a large volume, prefilled, ready-to-use feeding system to achieve delivery of noncontaminated product for up to 36 h hangtime.     

Primary focal segmental glomerulosclerosis: clinical course and response to therapy

Primary focal segmental glomerulosclerosis (FSGS) is a lesion associated with a poor prognosis and results in end-stage renal disease after 5 to 10 years. Based on past experience, many nephrologists have considered primary FSGS a lesion that is steroid resistant and therefore are reluctant to offer steroids as treatment. Recent data, however, have demonstrated that patients with primary FSGS have a response to steroid therapy that is considerably better than had been described. Thus, it may be that nephrologists have been more "steroid reluctant" than the lesion is steroid resistant. To better understand this issue we review the clinical course and response to therapy in patients with primary FSGS.     

Disruption of epithelial cell-matrix interactions induces apoptosis

Cell-matrix interactions have major effects upon phenotypic features such as gene regulation, cytoskeletal structure, differentiation, and aspects of cell growth control. Programmed cell death (apoptosis) is crucial for maintaining appropriate cell number and tissue organization. It was therefore of interest to determine whether cell-matrix interactions affect apoptosis. The present report demonstrates that apoptosis was induced by disruption of the interactions between normal epithelial cells and extracellular matrix. We have termed this phenomenon "anoikis." Overexpression of bcl-2 protected cells against anoikis. Cellular sensitivity to anoikis was apparently regulated: (a) anoikis did not occur in normal fibroblasts; (b) it was abrogated in epithelial cells by transformation with v-Ha-ras, v-src, or treatment with phorbol ester; (c) sensitivity to anoikis was conferred upon HT1080 cells or v-Ha-ras-transformed MDCK cells by reverse-transformation with adenovirus E1a; (d) anoikis in MDCK cells was alleviated by the motility factor, scatter factor. The results suggest that the circumvention of anoikis accompanies the acquisition of anchorage independence or cell motility.     

Transfer of loads between lumbar tissues during the flexion-relaxation phenomenon

STUDY DESIGN AND METHODS: This study used an anatomically detailed model of the lumbar tissues, driven from biologic signals of vertebral displacement and myoelectric signals, to estimate individual muscle and passive tissue force-time histories during the performance of the "flexion-relaxation" maneuver. Eight male university students performed three trials each of the "flexion-relaxation" maneuver with six pairs of surface myoelectric electrodes monitoring the right side of the trunk musculature, an electromagnetic device to record lumbar flexion, and videotape to record body segment displacement. OBJECTIVES: To examine the loads on individual tissues during the transfer of moment support responsibility from predominantly active muscle to predominantly passive tissue. SUMMARY OF BACKGROUND DATA: No previous studies, to the authors' knowledge, have examined individual tissue loading during the flexion-relaxation maneuver. RESULTS: Although most subjects were able to "relax" their lumbar extensors in full flexion, activity remained in the thoracic extensors and abdominals. Tissue load predictions suggested that while the lumbar extensor muscles were neurally "relaxed" (i.e., myoelectric silence), substantial elastic forces would assist the passive tissues in extensor moment support. On average, subjects sustained almost 3 kN in compressive load on the lumbar spine and about 755 N of anterior shear during full flexion with only 8 kg held in the hands. CONCLUSIONS: The "relaxation" of lumbar extensor muscles appeared to occur only in an electrical sense because they generated substantial force elastically through stretching. Loading of the interspinous and supraspinous ligaments, in particular, was high relative to their failure tolerance.