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PubMed1991

Isolation and characterization of insertion mutants in E1A of adenovirus type 5.

We have constructed a series of insertion mutations at 18 sites in the coding sequences of early region 1A (E1A) of human adenovirus type 5 (Ad5). At each site we have introduced three types of mutation: a 39-bp insertion specifying a 13-aa residue oligopeptide, a 39-bp insertion containing chain termination codons in all three reading frames, and a "collapsed" insert of 6-bp forming a conventional linker insertion mutation. All mutants were sequenced to determine the precise location, structure, and orientation of the inserts. The mutants were assayed for their abilities to trans-activate and to repress using transient expression assays in HeLa cells cotransfected with the E1A mutant plasmids and a reporter plasmid containing the bacterial beta-galactosidase (lac Z) gene under the control of Ad5 early promoters. The mutants were also tested for their ability to transform baby rat kidney cells in cooperation with either E1B or the ras oncogene. Each mutant was rescued into virus and infectivity was compared in HeLa and 293 cells. In addition, E1A protein synthesis was analyzed in cells infected with the mutant viruses and the insertions were found to have pronounced but unpredictable effects on electrophoretic mobility of E1A proteins in SDS-polyacrylamide gels. The results of functional assays indicated that only mutations mapping in, or deleting, the unique region of the 13 S mRNA product had any effect on ability to trans-activate and that a perfect correlation existed between ability of a mutant to trans-activate and to replicate efficiently in HeLa cells or to transform baby rat kidney cells in an E1A plus E1B mediated assay. In contrast, insertions near conserved region 2 of exon I and in the NH2-terminal portion of exon II significantly reduced repression activity but left transforming activity with E1B or with ras essentially unaffected suggesting that the repression function of E1A is separate from, or at least nonessential in, transformation.

Adenovirus Early Proteins↗
PubMed1984

Effects of transposable element insertions on RNA encoded by the white gene of Drosophila.

We have examined the manner in which transposable element insertions affect the expression of the white gene of Drosophila by analyzing polyadenylated RNA of flies with each of nine insertions in or near the gene. In five mutants having insertions in the transcribed sequences of white, transcripts initiating at the white promoter are truncated within the insertions. Two insertions in the 3 kb intron of white alter neither the amount nor the structure of the mature white RNA. An insertion near the 5' end of the gene blocks the accumulation of any white transcripts. Another insertion, located 1.2 kb upstream from the transcribed region of the gene, causes a mutant phenotype yet surprisingly has no obvious effect on the structure or abundance of the major white RNA. We also show that a mutation at each of two other loci that modulate the phenotype of the white-apricot insertion mutant are correlated with small but significant changes in the pattern of white transcripts.

Animals↗
PubMed1983

Transfer-defective and tetracycline-sensitive mutants of the incompatibility group HI plasmid R27 generated by insertion of transposon 7.

Transposon Tn7 insertion was used to obtain either transfer-defective (Tra-) or tetracycline-sensitive (Tc-) mutants of the HI incompatibility group (IncHI) plasmid R27. The 600 apparent R27::Tn7 derivatives fell into three classes: Tra-, Tc-, and Tra- Tc-. Mutants of R27 defective in the thermosensitive mode of transfer characteristic of IncH plasmids were obtained with transfer frequencies of less than 1 X 10(-8) transconjugants per recipient after 18 hr at 26 degrees C. These mutants, which were generated at a frequency of 1 per 100 insertions, were nonleaky and nonrevertible. Tc- mutants of R27, generated at a frequency of 0.5 per 100 insertions, were also nonrevertible. Loss of tetracycline resistance was associated with an increased frequency of transfer (average 3.6 X 10(-3) transconjugants per donor per hour at 30 degrees C) compared with transfer of the wild-type R27 plasmid (1.6 X 10(-8) per donor per hour). Tn7 insertions which generated Tc- or Tra- mutants of R27 had no effect on entry exclusion of other H group plasmids. The molecular weights of Tra- and Tc- R27::Tn7 derivatives were approximately 120.5 MDa, corresponding to the sum of R27 (112 MDa) and Tn7 (8.5 MDa). A third class of Tn7 insertion derivatives (Tra- Tc-) was obtained; however, strains expressing this phenotype were plasmid free, and appeared to have Tn7 integrated at a chromosomal site. Restriction digestion with XbaI and subsequent hybridization with ColE1::Tn7 were used to compare R27::Tn7 derivatives and to locate Tn7 insertion sites. Loss of tetracycline resistance was associated with Tn7 insertion into a 24-kb XbaI fragment of R27. Although loss of plasmid transfer in several R27::Tn7 derivatives was accompanied by insertion of Tn7 into a 14-kb XbaI fragment of the plasmid, these mutants had also undergone a small increase in the size of the 24-kb XbaI fragment of R27.

Conjugation, Genetic↗
PubMed1978

Heteroduplex electron microscopy of phage Mu mutants containing IS1 insertions and chloramphenicol resistance transposons.

We have examined by electron microscopy the DNA heteroduplexes of six bacteriophage Mu mutants, Mu X cam, generated by the insertion of the Tn9 transposon for chloramphenicol resistance. Tn9 was found to be 2.8 +/- 0.2 kilobases (kb) in length and to consist of a cam determinant flanked by two IS1 sequences arranged in a direct order. In two of the six Mu X cam mutants, the Tn9 insertion was at a fixed location, 3.9 kb from the left, or c, end. In the other four mutants, the position of the insertion varied, even though the lysogenic cultures induced were grown from single colonies. The insertion was located at either 3.3 kb, 3.9 kb, or, less frequently, at 4.4 kb from the left end of the DNA. Furthermore, at low frequencies, the insertions were found to be in an orientation opposite to what predominated in the preparation. Thus, Tn9 in the Mu X cam mutants examined could appear to undergo rapid rearrangements during Mu growth or over a few generations of cell growth. One of the Tn9 insertion sites was apparently the same as that for a 0.8 kb insertion found in a Mu X mutant. This latter insertion was identified as an IS1 sequence. The DNA molecules from all the Mu X cam mutant phage particles were found to be missing the bacterial DNA at the S (right) end, along with a variable amount of the adjoining Mu DNA in the beta region. This observation supports the headful packaging model for Mu DNA.

Chloramphenicol↗
PubMed1989

Insertional mutagenesis using a synthetic lac operator.

We have developed a novel cassette for generating insertion mutants in multi-copy bacterial plasmids. The cassette consists of synthetic oligodeoxyribonucleotides (oligos) which form a DNA duplex following reconstitution in vitro, due to sequence complementarity. It contains a 21-bp segment of the lac operator (lacZo), to provide a readily detectable phenotypic marker. Bacterial colonies harboring plasmids with insertions of this cassette are blue due to constitutive expression of the lac operon resulting from titration of lac repressor molecules by plasmid-borne lacZo sequences. Synthetic oligos containing a desire sequence may be added to the cassette by complementary ends for targeted insertion into plasmids. Sequencing of the resulting insertion mutants is facilitated by using oligos within the cassette as primers for bidirectional sequencing. This allows a complete characterization of each insertion in terms of location, structure of flanking sequences, and orientation of the inserted oligo. We have used this system to construct a series of mutants in early region 1a genes of human adenovirus type 5. For this purpose we designed a cassette which had all three possible translational reading frames open when inserted in one orientation, and all reading frames closed in the other orientation. The cassette also had BamHI restriction sites at each end which could be used to 'collapse' mutants, reducing the size of each insert to 6 bp.

Base Sequence↗
PubMed1995

Transfemoral insertion of a bifurcated endovascular graft for aortic aneurysm repair: the first 22 patients.

The purpose of this study was to evaluate and optimize a system of transfemoral bifurcated graft insertion for endovascular repair of infrarenal aortic aneurysm. Grafts were inserted through bilateral femoral arteriotomies in 22 patients. Placement was guided by fluoroscopy. Results were assessed by completion angiography, with computed tomography scanning or duplex ultrasonography at 1, 3 and 6 months. The first 11 insertions were complicated by failed insertion in two cases, proximal leakage in one, graft limb thrombosis in five and wound infection in one. The second 11 insertions were complicated by retrograde leakage around the distal graft orifice in two patients. One of these was associated with aneurysm rupture, leading to the sole mortality of the series. There were no instances of graft migration or embolism. In conclusion, the lessons learned during the first 11 insertions were responsible for the improved results apparent in the second 11 insertions. When applied in properly selected patients, transfemoral insertion of a bifurcated graft is a reliable method of isolating an aortic aneurysm from the circulation.

Aortic Aneurysm, Abdominal↗
PubMed2005

Insertion behavior of the Bacillus thuringiensis Cry4Ba insecticidal protein into lipid monolayers.

Toxicity mechanisms of Bacillus thuringiensis Cry insecticidal proteins involve membrane insertion and lytic pore formation in lipid bilayers of the target larval midgut cell membranes. The B. thuringiensis Cry4Ba mosquito-larvicidal protein has been shown to be capable of permeabilizing liposome vesicles and of forming ion channels in planar lipid bilayers. Here, the membrane interaction of the 65-kDa activated Cry4Ba protein with the lipid monolayers, comprising dipalmitoyl phosphatidylcholine, dioleoyl phosphatidylethanolamine, and cholesterol (Chol), was studied using Langmuir-Blodgett technique. The interactions of the Cry4Ba protein with the lipid monolayers were measured from the surface pressure versus area isotherms of the protein-lipid monolayers. The increase in the mean molecular area was demonstrated as an incorporation of the protein into lipid monolayers. The insertion of the Cry4Ba protein was monitored by measuring as an increase of the surface pressure at constant molecular area. For a given monolayer, the membrane insertion of the Cry4Ba reduced as the initial surface pressure increased. The Cry4Ba protein showed a strong preference of an insertion towards a Chol monolayer. In addition, the mixed monolayers of Chol showed an enhanced effect on the insertion kinetics of Cry4Ba into lipid films, suggesting its involvement in the modulation of the protein insertion. These findings provide the first evidence that the Cry4Ba protein is capable of inserting itself into lipid monolayers, depending on the packing density of the monolayers. Our results also indicate that only a limited part of the protein is likely to be involved in the insertion.

Animals↗
PubMed2004

Fertility in beef cattle given a new or previously used CIDR insert and estradiol, with or without progesterone.

The objective was to compare pregnancy rates following fixed-time AI (FTAI) in beef cattle given a new or previously used CIDR insert and injections of estradiol, with or without progesterone, to synchronize follicular wave emergence. In Experiment 1, heifers (n=616) received a new or once-used CIDR insert for 9 days and were given 1mg estradiol cypionate (ECP), with or without 100 mg of a commercial progesterone preparation (CP4), at CIDR insertion. Heifers were treated with PGF at CIDR removal and 0.5 mg ECP i.m. 24h later, with FTAI 55 to 60 h after CIDR removal. Pregnancy rate was not affected by either the number of CIDR uses (P=0.59; 48.3% versus 46.2% for new versus once-used CIDRs, respectively) or the addition of progesterone (P=0.42; 45.6% versus 48.8% for ECP+CP4 and ECP, respectively). In Experiment 2 (replicated at two locations), heifers (n=56) and lactating beef cows (n=307) received a once- or twice-used CIDR and an i.m. injection of 1mg estradiol benzoate (EB), with or without 100 mg progesterone, at CIDR insertion. Cattle received PGF in the ischiorectal fossa at CIDR removal (Day 7) and 1mg EB i.m. 24h later, with FTAI 52 to 56 h after CIDR removal. Pregnancy rate was affected by location (P<0.002; 46.0% versus 61.1% for Locations A and B, respectively), parity (P<0.04; 67.9% versus 53.1% in heifers and cows, respectively), and numbers of times the CIDR had been used (P<0.03; 62.4% versus 48.4% for once- and twice-used CIDRs, respectively). However, the addition of progesterone to the injection of EB at CIDR insertion did not affect pregnancy rate (P=0.6). In Experiment 3, heifers (n=187) received one new, one once-used, one twice-used or two twice-used CIDRs for 7 days and 2 mg EB plus 50 mg of CP4 at the time of CIDR insertion. Heifers were treated with PGF at CIDR removal and 1mg EB i.m. 24 h later, with FTAI 52-56 h after CIDR removal. Pregnancy rate was not affected by treatments (P=0.28, 57.5, 63.8, 47.9, 47.9% for one new, one once-used, one twice-used, or two twice-used CIDRs, respectively). In summary, pregnancy rate to FTAI did not differ between cattle synchronized with a new or once-used CIDR, but pregnancy rate was lower in cattle synchronized with a twice-used CIDR; however, the insertion of two twice-used CIDRs did not affect pregnancy rates. The addition of an injection of progesterone to the estradiol treatment at CIDR insertion did not enhance pregnancy rate to FTAI.

Administration, Intravaginal↗
PubMed2005

Effects of shoe inserts and heel height on foot pressure, impact force, and perceived comfort during walking.

Studying the impact of high-heeled shoes on kinetic changes and perceived discomfort provides a basis to advance the design and minimize the adverse effects on the human musculoskeletal system. Previous studies demonstrated the effects of inserts on kinetics and perceived comfort in flat or running shoes. No study attempted to investigate the effectiveness of inserts in high heel shoes. The purpose of this study was to determine whether increasing heel height and the use of shoe inserts change foot pressure distribution, impact force, and perceived comfort during walking. Ten healthy females volunteered for the study. The heel heights were 1.0cm (flat), 5.1cm (low), and 7.6cm (high). The heel height effects were examined across five shoe-insert conditions of shoe only; heel cup, arch support, metatarsal pad, and total contact insert (TCI). The results indicated that increasing heel height increases impact force (p<0.01), medial forefoot pressure (p<0.01), and perceived discomfort (p<0.01) during walking. A heel cup insert for high-heeled shoes effectively reduced the heel pressure and impact force (p<0.01), an arch support insert reduced the medial forefoot pressure, and both improved footwear comfort (p<0.01). In particular, a TCI reduced heel pressure by 25% and medial forefoot pressure by 24%, attenuate the impact force by 33.2%, and offered higher perceived comfort when compared to the non-insert condition.

Adult↗
PubMed2004

Knee-simulator testing of conventional and cross-linked polyethylene tibial inserts.

We compared the resistance to delamination and to adhesive/abrasive wear of conventional and highly cross-linked polyethylene tibial inserts of a cruciate-retaining total knee design using a knee simulator. Both groups were tested after aggressive, accelerated aging, and 1 set of conventional inserts was studied without aging. Aging oxidized the conventional, but not the highly cross-linked, inserts. The simulated normal gait testing lasted for 5 and 10 million cycles for the conventional and highly cross-linked inserts, respectively. Aged conventional inserts showed delaminations, whereas none were observed in the unaged conventional and aged cross-linked inserts. Wear rates measured by the gravimetric method were 9 +/- 2 mm3, 10 +/- 4 mm3, and 1 +/- 0 mm3 per million cycles; by the metrologic method, they were 8 +/- 1 mm3, 9 +/- 2 mm3, and 3 +/- 0 mm3 for the unaged conventional, aged conventional, and aged highly crosslinked inserts, respectively. In the test model used, oxidation led to delamination, whereas increased cross-link density resulted in reduced adhesive/abrasive wear of tibial inserts.

Equipment Failure Analysis↗
PubMed2004

Correlation of interference screw insertion torque with depth of placement in the tibial tunnel using a quadrupled semitendinosus-gracilis graft in anterior cruciate ligament reconstruction.

PURPOSE: To evaluate the insertion torque of a soft-tissue interference screw in relation to depth of insertion into the tibial tunnel when used for fixation of a quadrupled semitendinosus-gracilis autograft in anterior cruciate ligament reconstruction. TYPE OF STUDY: Biomechanical cadaver study. METHODS: Ten quadrupled semitendinosus-gracilis grafts were harvested from fresh-frozen cadaver knees and fixed in donor proximal tibias using 10-mm bioabsorbable interference screws (Arthrex, Naples, FL). A cannulated torque screwdriver was used to measure screw insertion torque at 3 depths in the tibial tunnel: the outer cortex (distal third), the articular surface (proximal third), and between these 2 points (middle third). RESULTS: The mean insertion torques for the distal third, middle third, and proximal third were 8.7, 4.7, and 4.3 in/lb, respectively. The insertion torque was significantly higher at the outer cortex (distal third) than the middle third and proximal third (joint line of the tibial tunnel) ( P < .05). CONCLUSIONS: Our results indicate a correlation between insertion torque and depth of placement of bioabsorbable interference screws used for fixation of a semitendinosus-gracilis graft. Lower insertion torque at the articular surface, resulting in lower peak load or pullout strength, may outweigh the proposed benefits of joint-line fixation of a semitendinosus-gracilis graft used for anterior cruciate ligament reconstruction. CLINICAL RELEVANCE: Studies have suggested that anatomic proximal fixation of ACL grafts in the tibial tunnel produces stability similar to intact knees. The results of our study indicate that lower insertion torque at the articular surface results in lower peak load and pullout strength of the graft, which may outweigh the proposed benefits of joint-line fixation.

Adult↗
PubMed2005

Influence of thread design on bioabsorbable interference screw insertion torque during retrograde fixation of a soft-tissue graft in synthetic bone.

PURPOSE: Bioabsorbable interference screw design may influence biomechanical characteristics. This study compared the insertion torque and load at failure characteristics of 2 types of screws during retrograde fixation of a soft-tissue graft. TYPE OF STUDY: Biomechanical study. METHODS: Eight matched pairs of doubled 100-mm long tibialis anterior allografts were prepared and fixed in appropriately sized tunnels created in 10 lb/ft 3 (0.16 g/cm3) dense synthetic bone blocks using screws of similar length and root and thread diameter designed with either a large buttress thread with a smaller taper or small buttress thread with a larger taper. Insertion torque was measured at one-third, two-thirds, and full screw insertion. After the graft fixation constructs were mounted in a servohydraulic-testing device with the loading axis aligned directly with the tunnel and preloaded to 25 N, they were cycled 3 times from 0 to 50 N, and then subjected to a 20 mm/minute traction force to failure. RESULTS: All constructs failed by graft slippage past the screw. Mean maximum load at failure (360.5 +/- 68 N v 341.6 +/- 58 N, P = .2) and stiffness (63.6 +/- 16 N/mm 2 v 66.4 +/- 14 N/mm 2 , P = .89) was similar between constructs fixed with a large buttress thread small-taper screw and small buttress thread large-taper screw, respectively. The small buttress thread screw with a large taper displayed greater mean insertion torque at one-third insertion (4.1 +/- 0.57 in-lb v 3.2 +/- 0.49 in-lb, P = .03), whereas the large buttress thread screw with a small taper displayed greater mean insertion torque at full insertion (11.1 +/- 0.74 in-lb v 9.4 +/- 1.3 in-lb, P = .012). Mean differences were not observed at two-thirds screw insertion (P = .12). CONCLUSIONS: Large buttress thread small-taper screws displayed biomechanical fixation characteristics comparable to small buttress thread large-taper screws. CLINICAL RELEVANCE: Given reports of superior screw-graft-bone tunnel contact area, these biomechanical results suggest that use of a large buttress screw with a small taper may be preferable for retrograde soft-tissue graft fixation.

Absorbable Implants↗
PubMed2007

Biomechanical analysis of differing pedicle screw insertion angles.

BACKGROUND: Pedicle screw fixation to stabilize lumbar spinal fusion has become the gold standard for posterior stabilization. A significant percentage of surgical candidates are classified as obese or morbidly obese. For these patients, the depth of the incisions and soft tissue makes it extremely difficult to insert pedicle screws along the pedicle axis. As such, the pedicle screws can only be inserted in a much more sagittal axis. However, biomechanical stability of the angled screw insertion has been controversial. We hypothesized that the straight or parallel screw was a more stable construct compared to the angled or axially inserted screw when subjected to caudal cyclic loading. METHODS: We obtained 12 fresh frozen lumbar vertebrae from L3 to L5 from five cadavers. Schantz screws (6.0 mm) were inserted into each pedicle, one angled and along the axis of the pedicle and the other parallel to the spinous process. Fluoroscopic imaging was used to guide insertion. Each screw was then subjected to caudal cyclic loads of 50 N for 2000 cycles at 2 Hz. Analysis of initial damage, initial rate of damage, and total damage during cyclic loading was undertaken. FINDINGS: Average total fatigue damage for straight screws measured 0.398+/-0.38 mm, and 0.689+/-0.96 mm for angled screws. Statistical analysis for total fatigue damage ratio of angled to straight screws revealed that a significant stability was achieved in straight-screw construct (P<0.03). INTERPRETATION: This study showed that straight screw insertion results in a more stable pedicle-screw construct. The angled screw insertion technique resulted in more scattered values of damage indicating that the outcome from the angled screw fixation is less predictable. This validates the use of this technique to implant pedicle screws across the axis of the pedicle (parallel to the mid sagittal line) rather than along the axis, and has broad implications in instrumented posterior lumbar spinal surgery.

Adult↗
PubMed1990

Vibrational fluctuations of hydrogen bonds in a DNA double helix with alternating TA type inserts.

The Green's function technique is applied to a study of breathing modes in a DNA double helix which contains a region of different base pairs from the rest of the double helix. The calculation is performed on an alternating poly(dC-dG).poly(dC-dG) helix in the B conformation with four consecutive base pairs replaced by a model of a biological promoter region with four alternating T-A,A-T base pairs, henceforth referred to as (TATA)2. The average stretch of interbase hydrogen bonds is found to be amplified around the insert. This is likely related to the (TATA)2 insert having a lower stability against hydrogen bond melting than the two semi-infinite poly(dC-dG).poly(dC-dG) helices. The insert region may be considered to be a site of enhanced tendency to melt in such a helix. The results show that an alternating AT insert of four base pairs has a larger average hydrogen bond stretch inside and outside the insert region than the average hydrogen bond stretch inside and outside an insert of four consecutive A-T base pairs, henceforth referred to as (AAAA).(TTTT). Calculations are performed which show that the enhancement of the average hydrogen bond stretch around an alternating TA type insert is greatly dependent upon the local modes and not the inband modes. The amount of local mode enhanced average stretch is explored as a function of insert size.

Adenine↗
PubMed2004

Pancreatic stent insertion: consequences of failure and results of a modified technique to maximize success.

BACKGROUND: Increasingly, pancreatic stents are being placed to prevent post-ERCP pancreatitis. However, guidewire and stent placement may fail if the duct is small or tortuous, potentially exacerbating the risk. This study assessed the impact of unsuccessful pancreatic stent placement on complications and the efficacy of a modified technique for stent insertion when pancreatic ductal anatomy makes stent insertion technically difficult. METHODS: Technical variables and 30-day complications of consecutive therapeutic ERCPs, including attempted major papilla pancreatic stent insertion were prospectively studied. Success rates for pancreatic stent placement were compared for a 1-year period during which conventional deep guidewire insertion was used and another 1-year period in which a modified technique was used as needed in patients with ductal anatomy that made stent placement technically difficult. In the modified technique, a short (2-3 cm) small diameter (3F-5F) stent was placed over a 0.018-in nitinol-tipped guidewire, passed as little as 1 to 2 cm beyond the pancreatic sphincter. RESULTS: In 225 high-risk therapeutic ERCPs, pancreatitis occurred after the procedure in two of 3 (66.7%) patients in whom pancreatic stent insertion failed vs. 32 of 222 (14.4%) patients with successful insertion (p=0.06). Severe pancreatitis occurred only after unsuccessful stent insertion. Significant multivariate risk factors for post-ERCP pancreatitis were unsuccessful pancreatic stent insertion (odds ratio 16.1: 95% CI[1.3, 200]), sphincter of Oddi dysfunction (odds ratio 3.2: 95% CI[1.4, 7.5]), and prior post-ERCP pancreatitis (odds ratio 3.2: 95% CI[1.4, 7.1]). The following were not risk factors: performance of pancreatic, biliary, or needle-knife pre-cut sphincterotomy; number of pancreatic contrast injections; and difficult cannulation. Stent placement was unsuccessful in 3 (3.2%) of 93 attempts during the 1-year period in which a conventional technique was used vs. none of 132 attempts in a subsequent year in which the modified technique was used. CONCLUSIONS: Failed attempts at pancreatic stent placement are associated with an extremely high risk of post-ERCP pancreatitis. Success can be consistently achieved by use of a modified technique.

Adult↗
PubMed1999

Complications of percutaneous insertion of Hickman catheters in children.

BACKGROUND/PURPOSE: The aim of this study was a retrospective evaluation of insertion and management complications of percutaneous Hickman catheter lines in pediatric patients to investigate whether the complication rate is acceptable in comparison with other insertion methods or other age groups. METHODS: Over a period of 22 months a total of 27 Hickman catheters were inserted in 22 pediatric patients (20 oncological, 2 nononcological; age 6 weeks to 17.5 years). RESULTS: Twenty-three of 36 insertion attempts (63.9%) were successful at first attempt. In another 4 patients, catheters were placed after repeated attempts. In an additional 4 patients, catheters were inserted by surgeons after percutaneous insertion failed. As immediate complications, 1 pneumothorax and 1 malposition were seen. Late complications included 1 to 29 (median, 8) days of fever in 15 patients, corresponding to 53 of 1,000 catheter days. Fourteen patients showed 21 positive blood cultures, including 11 cases of Staphylococcus epidermides, which might be related to the catheter. Antibiotics were given for a total of 1 to 130 (median, 35) days, that is 205 of 1,000 catheter days. No catheter was removed because of infectious complications. The total life span of the Hickman catheters was 1 to 371 (median, 163) days, the patients were in the hospital from 1 to 351 (median, 102) days because of their underlying disease. At the end of the study period, 8 of 27 (29.6%) catheters remained functioning in situ; 9 (33.3%) had been selectively removed. Two patients died with the catheter (7.4%) functioning well. Another 2 patients showed catheter thrombosis. Six catheters (22.2%) in 5 patients showed inadvertent dislodgement. CONCLUSION: Percutaneous Hickman catheter insertion in pediatric patients is effective; however, complication rate is relevant, but not higher than percutaneous insertion of subclavian vein or Hickman catheters in adults.

Adolescent↗
PubMed2001

Relevance of polymer molecular weight to the in vitro/in vivo performances of ocular inserts based on poly(ethylene oxide).

A previous study of the present authors on gel-forming erodible inserts, based on high molecular weight (MW, 400 kDa) poly(ethylene oxide) (PEO), for ocular controlled delivery of ofloxacin (OFX) has been extended to investigate the effects of PEO MW, in the 200-2000 kDa range, on insert properties relevant to therapeutic efficacy. Mucoadhesion has shown a dependence on MW, with a maximum for PEO 400. The in vitro drug release from inserts based on PEO 200, PEO 400 and PEO 900 was mainly controlled by insert erosion, whereas with PEO 2000 it was mainly diffusion-controlled in a first phase, followed by an erosion-controlled phase. The erosion time scale depended directly on MW. Immediately after application in the lower conjunctival sac of the rabbit eye, the inserts based on PEO of whichever MW formed mucoadhesive gels, well tolerated by the animals; then the gels spread over the corneal surface and eroded. PEO 2000 was unsuitable as an insert material, since the resulting gel spilled from the eye, due to excessive swelling. The gel residence time in the precorneal area, the drug permanence time in the aqueous humor at concentrations > MIC and the time to reach the maximal drug concentration in the aqueous humor (C(max)) depended directly on MW, indicating that transcorneal absorption was governed by gel erosion. All inserts increased Cmax and AUCeff (AUC for concentrations > MIC) with respect to the commercial eyedrops. The increases caused by PEO 400 and PEO 900 were similar (3.78- and 3.16-fold, respectively, for Cmax; 11.06- and 12.37-fold, respectively, for AUCeff), whereas smaller increases were produced by PEO 200. The PEO 400 and PEO 900 inserts have shown a potential for a topical treatment of endophthalmitis.

Animals↗
PubMed1999

Deep venous thrombosis after percutaneous insertion of vena caval filters.

PURPOSE: A large multicenter study has recently questioned the overall clinical efficacy of vena caval filters, especially when inserted prophylactically, because of the subsequent development of deep venous thrombosis (DVT) at the insertion site. We examined the incidence of this complication with newer, smaller diameter percutaneous devices. METHODS: We reviewed our vascular surgery and interventional radiology clinical registries to identify patients in whom a femoral percutaneous vena caval filter had been placed from 1993 to 1998. This list was cross referenced with patients who had undergone lower extremity venous ultrasound scan examinations for the diagnosis of DVT in the vascular laboratory within a 60-day period before and after the insertion of the filter device. RESULTS: A total of 35 patients during this 5-year period had timely follow-up venous duplex scan studies performed. The indications for filter placement were DVT in 16 patients (46%), pulmonary embolus in 13 patients (37%), DVT and pulmonary embolus in three patients (9%), and prophylactically in three patients (9%) at high risk for thromboembolization. Of the patients with documented thromboembolic events, 91% (29 of 32) had contraindications to anticoagulation therapy, and the remaining 9% (3 of 32) represented failure of anticoagulation therapy. A Greenfield filter was used in 13 patients (37%), a Simon Nitinol filter was used in 11 patients (31%), and a VenaTech filter was used in nine patients (26%). The other two patients (6%) had a Bird's Nest filter inserted. At a mean follow-up period of 12 +/- 2 days (median, 6 days), there was a 40% (14 of 35) incidence of proximal DVT in venous segments without evidence of thrombus before filter insertion. The majority (71%; 10 of 14) occurred in the common femoral vein, with three located in the superficial femoral vein and one in the external iliac vein. The lowest incidence of DVT was seen with the Greenfield and Bird's Nest filters as compared with the smaller Simon Nitinol and VenaTech filters (20% vs 55%; P < .05). The highest incidence of thrombosis occurred in patients with pre-insertion pulmonary emboli (50%; 8 of 16) as compared with those patients with DVT (38%; 6 of 16) and prophylactic insertion (0%; 0 of 3). However, the subgroups were too small to attain statistical significance. CONCLUSION: There is a continuing and significant incidence of new DVT development ipsilateral to the percutaneous femoral insertion site of vena caval filters. The smaller diameter filters are not associated with a lower incidence of femoral thrombosis.

Anticoagulants↗