Biomedical subjects

Xin Li

Publications and source records attributed to Xin Li.

At least 217 records · Page 12Linked to original sources

PubMed2004

Changes of tumor microcirculation after transcatheter arterial chemoembolization: first pass perfusion MR imaging and Chinese ink casting in a rabbit model.

AIM: To observe the change of tumor microcirculation after transcatheter arterial chemoembolization (TACE) with bletilla microspheres by using first pass perfusion MR imaging (FP) and Chinese ink casting. METHODS: VX2 carcinoma cells were surgically implanted into the left and right lobes of liver of 30 New Zealand white rabbits, which were divided into 3 groups at random. Emulsion of lipiodol mixed with mitomycin C, and 5-FU bletilla microspheres were injected into the hepatic artery respectively, and saline was used as control agent. MR imaging was performed with turbo-flash sequence 14 d after tumor implantation and 7 d after interventional therapy. The steepest slopes (SS) of the signal intensity versus time curves were created for quantitative analysis, 7.5% Chinese ink gelatin solution was injected through ascending artery (17 cases) or portal vein (2 cases) for lesion microvessel area (MVA) measurement after the last MRI examination. The correlation between perfusion imaging and MVA was studied blindly. RESULTS: The SS values at the rim of tumor in lipiodol group (mean, 49% per second) and bletilla group (mean, 35% per second) were significantly decreased (P<0.05) as compared with control group (mean, 124% per second), no difference was found between lipiodol and bletilla groups (P>0.05). In lipiodol group, the MVAs (24 974+/-11 836 microm(2)) in the center of the tumor were significantly smaller than those of the control group (35 510+/-15 675 microm(2)) (P<0.05), while the MVAs (80 031+/-22 745 microm(2)) around the tumor were significantly increased because small and dense plexuses appeared around the tumor which correlated to intense reaction of granulation tissue. None of the vessels was seen in the tumor in bletilla group, the peripheral MVAs of the tumor were significantly smaller than those of the control group (P<0.05) and lipiodol group (P<0.05). There was a good correlation between SS and MVAs in control group (r(s), 0.985, P<0.0001) and bletilla group (r(s), 0.743, P<0.05), the correlation was not significant in lipiodol group (r(s), 0.527, P>0.05). CONCLUSION: TACE with bletilla microspheres may enhance its anti-tumor effect by inhibiting the angiogenesis, and FP-MRI provides useful information to assess the TACE effect by depicting tumor vascularization and perfusion.

Animals↗

PubMed2004

Immune tolerance in pancreatic islet xenotransplantation.

AIM: To observe the effect of tail vein injection with donor hepatocytes and/or splenocytes on the islet xenotransplantation rejection. METHODS: New-born male pigs and BALB/C mice were selected as donors and recipients respectively. Islet xenotransplantation was performed in recipients just after the third time of tail vein injection with donor hepatocytes and/or splenocytes. Macrophage phagocytosis, NK(natural killing cell) killing activity, T lymphocyte transforming function of spleen cells, antibody forming function of B lymphocytes, and T lymphocyte subsets were taken to monitor transplantation rejection. The effects of this kind of transplantation were indicated as variation of blood glucose and survival days of recipients. RESULTS: The results showed that streptozotocin (STZ) could induce diabetes mellitus models of mice. The pre-injection of donor hepatocytes, splenocytes or their mixture by tail vein injection was effective in preventing donor islet transplantation from rejection, which was demonstrated by the above-mentioned immunological marks. Each group of transplantation could decrease blood glucose in recipients and increase survival days. Pre-injection of mixture of donor hepatocytes and splenocytes was more effective in preventing rejection as compared with that of donor hepatocyte or splenocyte pre-injection respectively. CONCLUSION: Pre-injection of donor hepatocytes, splenocytes or their mixture before donor islet transplantation is a good way in preventing rejection.

Animals↗

PubMed2004

High-resolution prediction of protein helix positions and orientations.

We have developed a new method for predicting helix positions in globular proteins that is intended primarily for comparative modeling and other applications where high precision is required. Unlike helix packing algorithms designed for ab initio folding, we assume that knowledge is available about the qualitative placement of all helices. However, even among homologous proteins, the corresponding helices can demonstrate substantial differences in positions and orientations, and for this reason, improperly positioned helices can contribute significantly to the overall backbone root-mean-square deviation (RMSD) of comparative models. A helix packing algorithm for use in comparative modeling must obtain high precision to be useful, and for this reason we utilize an all-atom protein force field (OPLS) and a Generalized Born continuum solvent model. To reduce the computational expense associated with using a detailed, physics-based energy function, we have developed new hierarchical and multiscale algorithms for sampling the helices and flanking loops. We validate the method using a test suite of 33 cases, which are drawn from a diverse set of high-resolution crystal structures. The helix positions are reproduced with an average backbone RMSD of 0.6 A, while the average backbone RMSD of the complete loop-helix-loop region (i.e., the helix with the surrounding loops, which are also repredicted) is 1.3 A.

Algorithms↗

PubMed2004

Study on the toxic effects induced by different arsenicals in primary cultured rat astroglia.

Arsenic toxicity is a global health problem affecting millions of people. The objectives of this study were to determine if the toxic effects on primary cultured rat astroglia would be induced by different arsenicals. Based on alamarBlue assay and the single cell gel electrophoresis (SCGE, comet assay), the cell viability and DNA damage in the cells exposed to different arsenicals were evaluated. Treatment of astroglia with methylated arsenicals, that is, pentavalent monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV), resulted in no obvious changes in cell viability and DNA damage at micromolar concentrations. However, treatment of astroglia with inorganic arsenicals, that is, arsenite and arsenate, caused decreased cell viability and increased DNA damage at micromolar levels, and showing a dose-related decrease in mean alamarBlue reduced rate and a dose-related increase in mean comet length. Our study is therefore highly suggestive for a link between inorganic exposure and cellular toxicity or DNA damage. Based on the results of this study, the toxic effects induced by arsenite were stronger than those induced by arsenate.

Animals↗

PubMed2004

Construction of a metastasis-associated gene subtracted cDNA library of human colorectal carcinoma by suppression subtraction hybridization.

AIM: To construct a differentially-expressed gene subtracted cDNA library from two colorectal carcinoma (CRC) cell lines with different metastatic phenotypes by suppression subtractive hybridization. METHODS: Two cell lines of human CRC from the same patient were used. SW620 cell line showing highly metastatic potential was regarded as tester in the forward subtractive hybridization, while SW480 cell line with lowly metastatic potential was treated as tester in the reverse hybridization. Suppression subtractive hybridization (SSH) was employed to obtain cDNA fragments of differentially expressed genes for the metastasis of CRC. These fragments were ligated with T vectors, screened through the blue-white screening system to establish cDNA library. RESULTS: After the blue-white screening, 235 white clones were picked out from the positive-going hybridization and 232 from the reverse. PCR results showed that 200-700 bp inserts were seen in 98% and 91% clones from the forward and reverse hybridizations, respectively. CONCLUSIONS: A subtractive cDNA library of differentially expressed genes specific for metastasis of CRC can be constructed with SSH and T/A cloning techniques.

Cell Line, Tumor↗

PubMed2004

[The effect of IRESSA on H22 mouse hepatocellular carcinoma].

OBJECTIVE: To investigate the effect of IRESSA (gefitinib, ZD1839) on H22 murine hepatocellular carcinoma. METHODS: Mice bearing H22 hepatocellular carcinoma were randomly divided into oral control group, Normal saline (NS) control group, cisplatin (CDDP) d1-5 group, CDDP d6-10 group, IRESSA group, IRESSA combined with CDDP early (IRESSA + CDDP d1-5) group, and IRESSA combined with CDDP lately (IRESSA + CDDP d6-10) group. IRESSA was given by daily gastrogavage for 10 days (day 1-day 10) at 100 mg/kg in body weight (BW). CDDP was given by daily intraperitoneal injection for 5 days (day 1-day 5, or day 6-day 10) at 1.2 mg/kg in BW. The growth inhibiting rate (IR) of tumor, change of BW, spleen index (SI), and amounts of blood leucocyte or hemoglobin were detected. RESULTS: IR of tumor in IRESSA group was not significantly difference with that in CDDP d1-5 group, CDDP d6-10 group, IRESSA + CDDP d1-5 group (P > 0.05). IR of tumor in IRESSA group, CDDP d1-5 group, CDDP d6-10 group, IRESSA and IRESSA + CDDP d1-5 group were 41%, 54%, 46%, and 56%, respectively. IR of tumor in IRESSA + CDDP d6-10 group (26%) was significantly lower than that in CDDP d6-10 group (P < 0.05) or in IRESSA + CDDP d1-5 group (P < 0.01). Compared with oral or NS control groups, SI and net BW in IRESSA group was not significantly difference (P > 0.05). SI and net BW in both IRESSA + CDDP d1-5 group and IRESSA + CDDP d6-10 group were lower markedly than those in IRESSA group (P < 0.01). CONCLUSION: Tumor growth of H22 bearing mice was markedly inhibited by IRESSA.

Animals↗

PubMed2004

Assessment of hepatocellular carcinoma vascularity before and after transcatheter arterial chemoembolization by using first pass perfusion weighted MR imaging.

AIM: To assess the vascularity of hepatocellular carcinoma (HCC) before and after transcatheter arterial chemoembolization (TACE) with the quantitative parameters obtained by first pass perfusion weighted MR imaging (FP-MRI). METHODS: Seventeen consecutive patients with one to three lesions in liver underwent FP-MRI before treatment. FP-MRI was also performed one, three, six, nine months, and one year after TACE. The baseline signal intensity (S0) of pre-TACE and one month after TACE was analyzed, the vascularity of HCC assessed by steepest slope of the signal intensity versus time curves (SS) was blindly correlated with their DSA feature and clinical outcome. RESULT: No significant difference was found on baseline signal intensity (S0) between pre-TACE and one month after TACE (F=0.309, P=0.583), The SS (mean, 32% per second) of lesion one month after TACE was lower than that of pre-TACE (mean, 69% per second), but with no statistical significance (F=3.067, P=0.092). When local recurrence occurred, the time intensity curves became steeper. The vascularity of HCC before and after TACE graded by SS closely correlated with that by DSA (K=0.453, P<0.05). CONCLUSION: FP-MRI is a useful criterion for selecting effective interventional treatment for patients with HCC in their initial treatment and during follow up.

Adult↗

PubMed2004

Simultaneous determination of clozapine, olanzapine, risperidone and quetiapine in plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry.

UNLABELLED: Clozapine (CLZ), olanzapine (OLZ), risperidone (RIP) and quetiapine (QTP) have been widely used in the treatment of schizophrenia. However, no study (or little study) has been conducted to determine the four drugs simultaneously by the use of high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI). OBJECTIVE: To develop a sensitive method for simultaneous determination of CLZ, OLZ, RIP and QTP in human plasma by HPLC-MS/ESI. METHODS: The analytes were extracted twice by ether after samples had been alkalinized. The HPLC separation of the analytes was performed on a MACHEREY-NAGEL C(18) (2.0 mm x 125 mm, 3 microm, Germany) column, using water (formic acid: 2.70 mmol/l, ammonium acetate: 10 mmol/l)-acetonitrile (53:47) as mobile phase, with a flow-rate of 0.16 ml/min. The compounds were ionized in the electrospray ionization (ESI) ion source of the mass spectrometer and were detected in the selected ion recording (SIR) mode. RESULTS: The calibration curves were linear in the ranges of 20-1000 ng/ml for CLZ and QTP, 1-50 ng/ml for OLZ and RIP, respectively. The average extraction recoveries for all the four analysts were at least above 80%. The methodology recoveries were higher than 91% for the analysts. The intra- and inter-day R.S.D. were less than 15%. CONCLUSION: The method is accurate, sensitive and simple for routine therapeutic drug monitoring (TDM) and for the study of the pharmacokinetics of the four drugs.

Antipsychotic Agents↗

PubMed2004

Vascular endothelial growth factor antisense oligodeoxynucleotides with lipiodol in arterial embolization of liver cancer in rats.

AIM: Transcatheter arterial embolization (TAE) of the hepatic artery has been accepted as an effective treatment for unresectable hepatocellular carcinoma (HCC). However, embolized vessel recanalization and collateral circulation formation are the main factors of HCC growth and recurrence and metastasis after TAE. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. This study was to explore the inhibitory effect of VEGF antisense oligodeoxynucleotides (ODNs) on VEGF expression in cultured Walker-256 cells and to observe the anti-tumor effect of intra-arterial infusion of antisense ODNs mixed with lipiodol on rat liver cancer. METHODS: VEGF antisense ODNs and sense ODNs were added to the media of non-serum cultured Walker-256 cells. Forty-eight hours later, VEGF concentrations of supernatants were detected by ELISA. Endothelial cell line ECV-304 cells were cultured in the supernatants. Seventy-two hours later, growth of ECV-304 cells was analyzed by MTT method. Thirty Walker-256 cell implanted rat liver tumor models were divided into 3 groups. 0.2 mL lipiodol (LP group, n=10), 3OD antisense ODNs mixed with 0.2 mL lipiodol (LP+ODNs group, n=10) and 0.2 mL normal saline (control group, n=10) were infused into the hepatic artery. Volumes of tumors were measured by MRI before and 7 d after the treatment. VEGF mRNA in cancerous and peri-cancerous tissues was detected by RT-PCR. Microvessel density (MVD) and VEGF expression were observed by immunohistochemistry. RESULTS: Antisense ODNs inhibited Walker-256 cells' VEGF expression. The tumor growth rate was significantly lower in LP+ODNs group than that in LP and control groups (140.1+/-33.8%, 177.9+/-64.9% and 403.9+/-69.4% respectively, F=60.019, P<0.01). VEGF mRNAs in cancerous and peri-cancerous tissues were expressed highest in LP group and lowest in LP+ODNs group. The VEGF positive rates showed no significant difference among LP, control and LP+ODNs groups (90%, 70% and 50%, H=3.731, P>0.05). The MVD in LP+ODNs group (53.1+/-18.4) was significantly less than that in control group (73.2+/-20.4) and LP group (80.3+/-18.5) (F=5.44, P<0.05). CONCLUSION: VEGF antisense ODNs can inhibit VEGF expression of Walker-256 cells. It may be an antiangiogenesis therapy agent for malignant tumors. VEGF antisense ODNs mixed with lipiodol embolizing liver cancer is better in inhibiting liver cancer growth, VEGF expression and microvessel density than lipiodol alone.

Animals↗

PubMed2004

A novel phase-switching protecting group for multi-step parallel solution phase synthesis.

A new phase-tag 1 which facilitates the parallel solution phase synthesis of carboxylic acids, esters, and carboxamides is reported. The new phase tag assists compound purification by enabling the selective resin capture of reaction products in either a reversible pH dependent manner (solid-phase extraction), or irreversibly in a Diels-Alder reaction.

Journal Article↗

PubMed2004

Constrained quadratic correlation filters for target detection.

A method for designing and implementing quadratic correlation filters (QCFs) for shift-invariant target detection in imagery is presented. The QCFs are quadratic classifiers that operate directly on the image data without feature extraction or segmentation. In this sense the QCFs retain the main advantages of conventional linear correlation filters while offering significant improvements in other respects. Not only is more processing required for detection of peaks in the outputs of multiple linear filters but choosing the most suitable among them is an error-prone task. All channels in a QCF work together to optimize the same performance metric and to produce a combined output that leads to considerable simplification of the postprocessing scheme. The QCFs that are developed involve hard constraints on the output of the filter. Inasmuch as this design methodology is indicative of the synthetic discriminant function (SDF) approach for linear filters, the filters that we develop here are referred to as quadratic SDFs (QSDFs). Two methods for designing QSDFs are presented, an efficient architecture for achieving them is discussed, and results from the Moving and Stationary Target Acquisition and Recognition synthetic aperture radar data set are presented.

Journal Article↗

PubMed2004

Highly enantioselective Friedel-Crafts reaction of aromatic amines with ethyl glyoxylate catalyzed by chiral titanium(IV) complexes: practical synthesis of aminomandelic acid derivatives.

The asymmetric Friedel-Crafts reaction of a variety of N,N-dialkylanilines with ethyl glyoxylate has been achieved by the catalysis of titanium complexes of BINOL derivatives to give corresponding ethyl esters of p-N,N-dialkylaminomandelic acids in high yields (85-99%) and good to excellent enantioselectivities (80-96.6% ee) under the optimized reaction conditions, which has added a new catalyst for this class of reactions. The reaction could also be carried out at a reduced catalyst loading (1 mol %) in gram scale, which provided a practical synthesis of enantiopure aminomandelic acid derivatives.

Journal Article↗

PubMed2004

Enzymatic reaction of the immobilized enzyme on porous silicon studied by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry.

Desorption/ionization on silicon mass spectrometry (DIOS-MS) is a matrix-free technique that allows for the direct desorption/ionization of low-molecular-weight compounds with little or no fragmentation of analytes. This technique has a relatively high tolerance for contaminants commonly found in biological samples. DIOS-MS has been applied to determine the activity of immobilized enzymes on the porous silicon surface. Enzyme activities were also monitored with the addition of a competitive inhibitor in the substrate solution. It is demonstrated that this method can be applied to the screening of enzyme inhibitors. Furthermore, a method for peptide mapping analysis by in situ digestion of proteins on the porous silicon surface modified by trypsin, combined with matrix-assisted laser desorption/ionization-time of flight-MS has been developed.

Animals↗

PubMed2004

Construction of tree models for pathogenesis of nasopharyngeal carcinoma.

Pathogenesis of nasopharyngeal carcinoma (NPC) is a multistep and multipathway process that cannot be fully explained by a fixed linear progression model. We used distance-based and branching-tree methods to construct more general tree-like models for NPC carcinogenesis from 170 comparative genomic hybridization (CGH) samples previously published in five smaller studies. Imbalances were classified into "overlap regions," each containing the most commonly gained or lost band on each chromosome arm as well as adjacent bands that were gained or lost almost as often. The chromosome abnormalities associated with NPC were -3p26-13 (48.9%), -11q22-25 (38.1%), -16q12-24 (38.1%), -14q24-32 (32.4%), -13q21-32 (22.3%), -9p23-21(21.6%), +12p12 (46%), +12q13-15 (43.9%), +1q22-32 (33.1%), +3q13.1-26.2 (30.2%), and +8q22.1-24.2 (27.3%). NPC can be classified into two groups, one marked by +12p12 and +8q22.1-24.2 and the other by -3p26-13, -11q22-25, -14q24-32, and +1q22-32. The tree models predicted -3p26-13 and +12p12 as early events and +8q22.1-24.2 as a late event. The predictions for -3p26-13 and +8q22.1-24.2 were consistent with previous studies. The prediction for +12p12 is being reported for the first time. Many known NPC-related genes on chromosomal regions of these tree models are discussed, some of which may merit additional study. The potential applications of tree models are also discussed.

Carcinoma↗

PubMed2004

Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways.

We previously identified the major pathological changes in the respiratory and immune systems of patients who died of severe acute respiratory syndrome (SARS) but gained little information on the organ distribution of SARS-associated coronavirus (SARS-CoV). In the present study, we used a murine monoclonal antibody specific for SARS-CoV nucleoprotein, and probes specific for a SARS-CoV RNA polymerase gene fragment, for immunohistochemistry and in situ hybridization, respectively, to detect SARS-CoV systematically in tissues from patients who died of SARS. SARS-CoV was found in lung, trachea/bronchus, stomach, small intestine, distal convoluted renal tubule, sweat gland, parathyroid, pituitary, pancreas, adrenal gland, liver and cerebrum, but was not detected in oesophagus, spleen, lymph node, bone marrow, heart, aorta, cerebellum, thyroid, testis, ovary, uterus or muscle. These results suggest that, in addition to the respiratory system, the gastrointestinal tract and other organs with detectable SARS-CoV may also be targets of SARS-CoV infection. The pathological changes in these organs may be caused directly by the cytopathic effect mediated by local replication of the SARS-CoV; or indirectly as a result of systemic responses to respiratory failure or the harmful immune response induced by viral infection. In addition to viral spread through a respiratory route, SARS-CoV in the intestinal tract, kidney and sweat glands may be excreted via faeces, urine and sweat, thereby leading to virus transmission. This study provides important information for understanding the pathogenesis of SARS-CoV infection and sheds light on possible virus transmission pathways. This data will be useful for designing new strategies for prevention and treatment of SARS.

Adult↗

PubMed2004

Two distinct cytochrome P450 aromatases in the orange-spotted grouper (Epinephelus coioides): cDNA cloning and differential mRNA expression.

The cDNA sequences encoding two distinct cytochrome P450 aromatases, namely P450aromB and P450aromA, were isolated from brain and ovary cDNA libraries of the orange-spotted grouper, respectively. The P450aromB cDNA consists of 1892 bp, and the open reading frame (ORF) encodes a putative protein of 506 amino acids. The P450aromA cDNA consists of 1836 bp, and the ORF encodes a putative protein of 518 amino acids. Northern blot analysis revealed a transcript of about 1.9 kb for P450aromB in the brain and kidney, and 2.1 kb for P450aromA in the ovary. The expression of both P450aromB and P450aromA genes in different tissues was further examined using one-step RT-PCR followed by Southern blot analysis. High levels of P450aromB mRNA expression were detected in the olfactory bulb, forebrain, midbrain, hypothalamus, medulla, pituitary, gill filament, gill arch, kidney, muscle, adipose tissue, and blood cells, but low levels in the hindbrain and ovary. High levels of P450aromA mRNA expression were detected in the ovary, pituitary, gill filament, gill arch, and spleen, but low levels in the forebrain, hindbrain, hypothalamus, and blood cells. In addition, the expression of P450arom genes in the orange-spotted grouper of different gonadal stages as induced by 17 alpha-methyltestosterone (MT) was investigated. The mRNA expression of P450aromB in the hypothalamus was highest in the intersexual stage, whereas the mRNA expression of P450aromA in the gonads was highest in the female stage, decreased in the intersexual stage, and lowest in the male stage. Results from current study indicate that P450aromB and P450aromA genes of the orange-spotted grouper have distinct tissue patterns of mRNA expression, and both of them may be involved in the MT-induced sex change.

Amino Acid Sequence↗

PubMed2004

cDNA sequence and spatio-temporal expression of prolactin in the orange-spotted grouper, Epinephelus coioides.

The cDNA sequence encoding the prolactin (PRL) gene of the orange-spotted grouper was obtained by randomly sequencing its pituitary cDNA library. The full-length cDNA of orange-spotted grouper PRL consists of 1342 bp. The open reading frame encodes a protein of 212 amino acids, which consists of a putative signal peptide of 24 residues and a mature protein of 188 amino acids. Northern blot analysis identified a single transcript of 1.4 kb in the pituitary gland, indicating perhaps the presence of only one form of PRL in the orange-spotted grouper. The expression of PRL gene in different tissues and during embryonic development of orange-spotted grouper was determined using one-step RT-PCR followed by Southern blot analysis. In addition to the pituitary gland, high levels of PRL gene expression were detected in the olfactory bulb, forebrain, midbrain, hypothalamus, hindbrain, medulla, gill, spleen, and adipose tissue. Very low levels of expression were detected in the kidney, liver, and blood cells. The PRL gene was also expressed in the gonads, with the higher level of expression observed in the stage 3 as compared to stage 2 ovary. During embryonic development, mRNA for PRL was detected at all time points examined except at 2h 15min post-fertilization, and its expression peaked at 9h post-fertilization, at the time of neurulation. Results from the current study suggest that PRL may have important paracrine or autocrine roles in diverse tissue types, including the brain and the gonads, and during embryonic development of the orange-spotted grouper.

Amino Acid Sequence↗

PubMed2004

Alteplase for treatment of occluded peripherally inserted central catheters: safety and efficacy in 240 patients.

PURPOSE: Peripherally inserted central catheters (PICCs) have dramatically improved intravenous therapy, but thrombotic occlusion remains a common problem. Despite the popularity of PICCs, there are few prospective data on the use of fibrinolytic agents to salvage these particular devices. The purpose of this study was to evaluate the efficacy and safety of alteplase treatment. MATERIALS AND METHODS: A subgroup analysis was performed from a phase IIIB prospective, multicenter trial of 995 patients evaluating the use of alteplase to restore function in occluded venous catheters. Two hundred forty patients (126 men; mean age, 53.5 years; range, 2-90 y) with occluded single-lumen (n = 104) or double-lumen (n = 136) PICCs were identified and constitute the study population. Dysfunction was defined as the inability to withdraw 3 mL of blood. Alteplase (2 mg/2 mL) was instilled into the dysfunctional lumen and assessed at 30 and 120 minutes. If the lumen remained occluded, a second alteplase dose was instilled and assessed at 30 and 120 minutes. Patency was defined as the ability to withdraw 3 mL blood and infuse 5 mL of saline solution. The primary efficacy endpoint was the cumulative restored patency rate after a maximum of two doses of alteplase. The primary safety endpoint was the incidence of intracranial hemorrhage within 5 days of treatment. Serious adverse events were recorded for 30 days after treatment. RESULTS: The primary efficacy endpoint was 92.9% (95% CI: 88.8%, 95.8%). Cumulative efficacy 30 and 120 minutes after first and second doses were 59.4%, 81.1%, 89.1%, and 92.9%, respectively. The primary safety endpoint was 0.0%. One major hemorrhage was reported: a patient with acute flare of ulcerative colitis experienced hematochezia 3 days after treatment. One serious adverse event (fever) was attributed to study drug. CONCLUSIONS: Treatment with use of a maximum of two doses of alteplase is safe and effective in restoring function to occluded PICCs.

Adult↗