Developing and validating a nomogram for early predicting the need for intestinal resection in pediatric intussusception.

Purpose: Develop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis. Patients & methods: Children with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model. Results: A total of 547 cases were included in the final analysis, of which 414 had non-intestinal necrosis and 133 had intestinal necrosis and underwent intestinal resection. The training set consisted of 411 patients and the validation cohort included 136 patients. Through forward stepwise regression, four variables (duration of symptoms, C-reaction protein, white blood cells, ascites) were selected for inclusion in the nomogram with a concordance index 0.871 (95% confidence interval: 0.834-0.908). Conclusion: We developed a nomogram for predicting intestinal resection in children with intussusception suspecting intestinal necrosis after a failed air-enema based on multivariate regression. This nomogram could be directly applied to facilitate predicting intestinal resection in pediatric intussusception suspecting necrosis.

Asiatic acid alleviates liver fibrosis via multiple signaling pathways based on integrated network pharmacology and lipidomics.

Liver fibrosis is characterized by the abnormal deposition of the extracellular matrix with a severe inflammatory response and/or metabolic disorder. Asiatic acid (AA), a natural compound derived from Centella asiatica, exhibited potent anti-fibrosis effects. This investigation first confirmed the anti-fibrosis effects of AA in TGF-ß-LX-2 cells and CCl4-induced liver fibrosis mice, and then sought to elucidate a novel mechanism of action by integrating network pharmacology and lipidomics. Network pharmacology was used to find potential targets of AA, while lipidomics was used to identify differential metabolites between fibrosis and recovered cohorts. AA could suppress hepatic stellate cell activation in vitro and improve liver fibrosis in vivo. Network pharmacology unveiled the genes involved in pathways in cancer, peroxisome proliferators-activated receptors signaling pathway, and arachidonic acid metabolism pathway. Furthermore, five key genes were found in the both human and mouse databases, indicating that arachidonic acid metabolism was important. Changes in lyso-phosphocholine (22:5), prostaglandin F2α, and other related lipid metabolites also suggested the involvement of arachidonic acid metabolism the anti-fibrotic effect. In summary, our integrated strategies demonstrated that AA targeted multiple targets and impeded the progression of liver fibrosis by ameliorating arachidonic acid metabolism.

Haemostatic indexes for predicting intestinal necrosis in children with intussusception.

BACKGROUND: To determine risk factors for intestinal necrosis in intussusception cases among children with failed non-surgical reduction for intussusception. METHODS: Totally, 540 hospitalized individuals with unsuccessful air-enema reduction in our hospital between November 2010 and November 2020 were assessed in this retrospective study. The 540 intussusception cases were divided into the intestinal necrosis and non-intestinal necrosis groups. Haemostatic parameters, demographic and clinical features were assessed. Predictors of intestinal necrosis were examined by univariable and multivariable logistic regression analyses. RESULTS: Of the 540 patients included, 113 showed intestinal necrosis. This intestinal necrosis group had a longer duration of symptom or length of illness, younger ages, higher platelet counts, fibrinogen amounts and d-dimer levels (all P = 0.000) compared with the non-intestinal necrosis group. Multivariable analysis revealed that duration of symptom (odds ratio (OR) 1.12; 95% confidence interval (CI) 1.16-1.23, P = 0.000), fibrinogen (OR 1.26; 95% CI 1.10-1.31, P = 0.010) and d-dimer (OR 2.07; 95% CI 1.91-2.28, P = 0.000) independently predicted intestinal necrosis in individuals undergoing surgical reduction for intussusception. Receiver operating characteristic curve analysis showed that d-dimer amounts had the largest area under the curve for predicting intestinal necrosis. CONCLUSION: On admission, long duration of symptom, high fibrinogen and d-dimer levels are critical risk factors for intestinal necrosis development in children with unsuccessful non-surgical reduction. d-Dimer levels have the best predictive value for intestinal necrosis.

Clinical characteristics of Meckel diverticulum in children: A retrospective review of a 15-year single-center experience.

Meckel diverticulum is the most prevalent congenital abnormality of the gastrointestinal tract in children. The aim of this study was to review and analyze clinical data on the diagnosis and management of Meckel diverticulum in pediatric patients. The records of 102 pediatric patients (<14 years old) who underwent surgery for Meckel diverticulum at our institute between 2001 and 2015 were reviewed. Clinical, imaging, laboratory, surgical, and pathological data were recorded. The series comprised 65 males and 37 females with a median age of 5.6 years. Lower gastrointestinal bleeding was the most frequently identified clinical manifestation of Meckel diverticulum, and this manifestation was observed in 41 patients. Intussusception secondary to Meckel diverticulum was identified in 32 patients. Twelve patients presented clinical features of peritonitis; of these patients, 8 had perforated Meckel diverticulum and 4 had Meckel diverticulitis. In 10 patients, Meckel diverticulum was incidentally diagnosed during other surgeries, including appendectomy and neonatal enterostomy. Seven patients were diagnosed with intestinal obstruction. Technetium-99m pertechnetate imaging offered high diagnostic yield. Open surgery was performed on 59 patients, while a laparoscopic approach was employed in 35 patients. The remaining 8 patients did not undergo resection of the Meckel diverticulum. Histology revealed ectopic gastric mucosa in 42 patients (44.7%), ectopic pancreatic tissue in 35 patients (37.2%), mucosa of the small intestine in 15 patients (16.0%), and both gastric and pancreatic ectopic tissue in 2 patients (2.1%). All patients recovered uneventfully except 2 patients in whom an intestinal adhesion obstruction was identified after discharge. Meckel diverticulum had various clinical manifestations in children. Technetium-99m pertechnetate imaging may be useful for diagnosing Meckel diverticulum. Surgical excision of the Meckel diverticulum may be safe and effective in symptomatic patients, and relatively better outcomes can be achieved using this approach.

Clinical characteristics of intussusception secondary to pathologic lead points in children: a single-center experience with 65 cases.

OBJECTIVE: Intussusception secondary to pathologic lead points (PLPs) is a challenging condition for pediatric surgeons, and few studies have been published on this subject. The aim of this study was to review and analyze clinical data on the diagnosis and management of intussusception secondary to PLPs in children. METHODS: Between 2002 and 2016, a total of 65 pediatric patients with a diagnosis of intussusception secondary to PLPs were retrospectively reviewed. RESULTS: The series comprised 47 males and 18 females. The average age of the patients was 4.9 years old. All patients had typical clinical manifestations, and intussusception was proven by ultrasound. Fifty-one patients had recurrent intussusception, of whom 21 had one, 14 had two, 10 had three, and 6 had more than three. There were 20 episodes of recurrence within 24 h (39.2%), 15 episodes were found between 24 and 72 h (29.4%), and the remaining 31.4% (16/51) of recurrences occurred after 72 h. All patients received surgical intussusception reduction. Meanwhile, enterectomy was the procedure of choice in 55 patients, polypectomy in 5 patients, and cystectomy in 3 patients. The types of intussusception secondary to PLPs included small intestinal (n = 25), ileocolic (n = 19), ileocecal (n = 11), ileo-ileocolic (n = 9) and cecalcolic (n = 1). The types of PLPs included Meckel diverticulum (n = 32), intestinal duplication (n = 14), benign polyps (n = 5), malignant lymphoma (n = 4), Peutz-Jeghers syndrome (n = 3), mesenteric cyst (n = 3), intestinal wall hematoma of hemophilia (n = 2), allergic purpura (n = 1), and hamartoma (n = 1). All patients recovered well with no relapse during follow-up, except for one patient who had an intestinal obstruction from adhesions that occurred approximately 3 months after discharge and who was curable after conservative treatment. CONCLUSIONS: Intussusception secondary to PLPs tends to exhibit recurrence. There are various types of intussusception secondary to PLPs. It is necessary to improve auxiliary examinations to identify the etiology and avoid intraoperative omission. Surgical reduction of intussusception secondary to PLPs is the preferred clinical management.

Risk factors associated with intestinal necrosis in children with failed non-surgical reduction for intussusception.

BACKGROUND: Intestinal necrosis is the most serious complication of intussusception. The risk factors associated with intestinal necrosis in pediatric patients with intussusception have not been well characterized. OBJECTIVE: This study aimed to investigate the risk factors associated with intestinal necrosis in pediatric patients with failed non-surgical reduction for intussusception. METHODS: Hospitalized patients who failed the air-enema reduction for intussusception in the outpatient department and subsequently underwent surgery were retrospectively reviewed. All cases were categorized into two groups: intestinal necrosis group and non-intestinal necrosis group based on the surgical findings. Demographic and clinical features including the findings from the surgery were recorded and analyzed. Factors associated with intestinal necrosis were analyzed using univariate and multivariate unconditional logistic regression analyses. RESULTS: A total of 728 cases were included. Among them, 171 had intestinal necrosis at the time of surgery. The group with intestinal necrosis had a longer duration of symptom or length of illness (P = 0.000), and younger (P = 0.000) than the non-intestinal necrosis group. Complex/compound type of intussusceptions is more likely to have intestinal necrosis. Multivariate analysis showed that the presence of grossly bloody stool (OR = 2.12; 95% CI 1.19-3.76, P = 0.010) and duration of symptom (OR = 1.07; 95% CI 1.06-1.08, P = 0.000) were independent risk factors for intestinal necrosis in patients hospitalized for surgical reduction for intussusceptions. CONCLUSION: At time of admission, the presence of bloody stools and duration of symptom are the important risk factors for developing intestinal necrosis for those patients who failed non-surgical reduction. The length of illness has the highest sensitivity and specificity to correlate with intestinal necrosis. This finding may suggest that we should take the intussusception cases that have the longer duration of symptom directly to operation room for reduction.

[p16INK4a protein is a specific molecular biomarker of breast cancer].

OBJECTIVE: To investigate the expression of p16INK4a protein in breast cancer and analyze its clinical significance. METHODS: A total of 132 surgical specimens of primary breast cancer obtained between 2014 and 2015 were examined for expressions of ER, PR, CK5/6, Her-2 and p16INK4a proteins using immunohistochemistry. RESULTS: The breast cancer samples were classified into 5 molecular subtypes, namely Luminal A (58 cases), Luminal B (32 cases), Her-2-positive (21 cases), basal-like (12 cases) and normal-like (9 cases) types. p16INK4a expression was negative in 7/132 (5.30%) cases, weakly positive in 15/132 (11.36%) cases, positive in 40/132 (30.30%) cases, and strongly positive in 70/132 (53.03%) cases. When categorizing negative and weakly positive cases into negative group and the positive and strongly positive cases into positive group, the total negative and positive expression rates of p16INK4a were 16.67% (22/132) and 83.33% (110/132) in the carcinoma tissues. Statistical analysis showed the expression intensity of p16INK4a differed significantly between the age groups (P<0.05) but was not significantly correlated with ER, PR, Her-2, molecular subtypes or metastasis of the tumors. CONCLUSION: The compensatory high expression of p16INK4a is the main mechanism of cell cycle deregulation in invasive breast cancer and can be an important specific molecular marker for invasive breast cancer.

Inhibition of p38 mitogen-activated protein kinase attenuates butyrate-induced intestinal barrier impairment in a Caco-2 cell monolayer model.

OBJECTIVES: Butyrate is well known to induce apoptosis in differentiating intestinal epithelial cells. The present study was designed to examine the role of p38 mitogen-activated protein kinase (MAPK) in butyrate-induced intestinal barrier impairment. METHODS: The intestinal barrier was determined by measuring the transepithelial electrical resistance (TER) in a Caco-2 cell monolayer model. The permeability was determined by measuring transepithelial passage of fluorescein isothiocyanate-conjugated inulin (inulin-FITC). The morphology of the monolayers was examined with scanning electron microscopy. The apoptosis status was determined by annexin V-FITC labeling and flow cytometry. The activity of p38 MAPK was determined by the phosphorylation status of p38 with Western blotting. RESULTS: Butyrate at 5 mM increases the apoptosis rate of Caco-2 cells and induces impairment of intestinal barrier functions as determined by decreased TER and increased inulin-FITC permeability. Butyrate treatment activates p38 MAPK in a concentration- and time-dependent manner. SB203580, a specific p38 inhibitor, inhibits butyrate-induced Caco-2 cell apoptosis. Treatment of SB203580 significantly attenuates the butyrate-induced impairment of barrier functions in the Caco-2 cell monolayer model. CONCLUSIONS: p38 MAPK can be activated by butyrate and is involved in the butyrate-induced apoptosis and impairment of intestinal barrier function. Inhibition of p38 MAPK can significantly attenuate butyrate-induced intestinal barrier dysfunction.

Catheter-directed thrombolysis and stenting in the treatment of iliac vein compression syndrome with acute iliofemoral deep vein thrombosis: outcome and follow-up.

BACKGROUND: The purpose of this study was to evaluate the safety and effectiveness of catheter-directed thrombolysis (CDT) and stenting in the treatment of iliac vein compression syndrome (IVCS) with acute iliofemoral deep vein thrombosis (DVT). METHODS: A retrospective analysis was conducted in 61 patients (36 women, 25 men, age range 32-90 years, mean 64 years) who had IVCS with acute iliofemoral thrmobosis (≤10 days) and were treated by CDT and stenting between June 2006 and August 2011. All patients presented with IVCS with a median duration of 4.1 days and were treated with CDT (urokinase: initial dose of 125,000-250,000 U followed by 20,000-60,000 U/hr) followed by stent placement. Filters were implanted in those patients with existing pulmonary embolism (PE), inferior caval vein thrombosis, or in accordance with the patients' request. The patency, the pressure gradient crossing the stenosis of the iliac vein, both thigh and calf limb circumferences, and complications were assessed before and after CDT and stenting. A Duplex ultrasound was used to perform follow-up examinations at 1 month, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years after the operation. RESULTS: Three patients had PE before CDT as assessed by the computed tomography angiography. A total of 28 patients had a filter implanted (25 patients had a Cordis permanent filter and 3 patients had a Braun temporary filter). A total of 68 stents were implanted in 61 patients. Overall, the 1-month, 6-month, 1-year, 2-year, 3-year, and 5-year primary patency rates were 96.7%, 95.1%, 91.8%, 90.2%, 88.5%, and 85.2%, respectively. The pressure gradient crossing the stenosis of the iliac vein decreased significantly after CDT and stenting (7.22 ± 4.64 vs. 1.82 ± 2.78 cm H2O, P < 0.001). The reductions of thigh and calf circumferences were 66.7% (6.19 ± 2.67 vs. 1.98 ± 1.43 cm) and 61.6% (4.36 ± 2.10 vs. 1.46 ± 1.10 cm), respectively. Reocclusion occurred in 7 patients within 1-27 months. Four patients (7%) experienced minor bleeding and were treated successfully with sandbag compression. One patient felt light pain on the left waist after 3 months of stenting. No large hematoma, stent migration, or acute thrombosis complications occurred during the procedure. Two patients died from nonvascular causes during a follow-up of 2-62 months (mean, 31.0 months). Four patients were found with limb swelling and three patients felt heaviness. The incidence rate of postthrombotic syndrome was 11.5% (7/61). CONCLUSIONS: Treatment with CDT for IVCS with acute DVT achieves good patency and vein function after 5 years of follow-up in this study. However, further evidence is required to establish longer term benefits.

[Retrograde tibial approach for endovascular recanalization of popliteal and tibioperoneal artery occlusion].

OBJECTIVES: To describe a procedure of the retrograde approach for endovascular treatment of complex popliteal and/or infrapopliteal occlusions and to determine its safety and efficacy in minimizing failure rates. METHODS: Between January 2010 and March 2012, 28 patients (16 male and 12 female patients) received retrograde tibial approach after failure of antegrade intervention. There were 3 patients with severe claudication (Rutherford category 3) and 25 patients with critical limb ischemia (Rutherford category 4 to 6). From this group, two techniques were employed. Twenty-four patients were treated via a retrograde transpedal access site and 4 patients via a transcollateral loop technique. The clinical and follow-up data of these patients were analyzed retrospectively. RESULTS: The technique success rates were 92.8% (26/28). No major complications and 3 (10.7%) minor sequelaes were documented in this study. Twenty-three patients were followed up for 3 to 29 months, with a mean of (14 ± 9) months. Overall patency was 73.9% (17/23) and 47.8% (11/23) at 6 and 12 months. Overall survival and limb salvage was 95.7% (22/23), ulcer were healed in 9/10 patients. CONCLUSION: The use of retrograde tibial or pedal approach seems feasible and safety in case of failure in antegrade revascularization of popliteal and/or infrapopliteal occlusions.

Bacterial colonization and intestinal mucosal barrier development.

The intestinal tract is colonized soon after birth with a variety of ingested environmental and maternal microflora. This process is influenced by many factors including mode of delivery, diet, environment, and the use of antibiotics. Normal intestinal microflora provides protection against infection, ensures tolerance to foods, and contributes to nutrient digestion and energy harvest. In addition, enteral feeding and colonization with the normal commensal flora are necessary for the maintenance of intestinal barrier function and play a vital role in the regulation of intestinal barrier function. Intestinal commensal microorganisms also provide signals that foster normal immune system development and influence the ensuing immune responses. There is increasingly recognition that alterations of the microbial gut flora and associated changes in intestinal barrier function may be related to certain diseases of the gastrointestinal tract. This review summarizes recent advances in understanding the complex ecosystem of intestinal microbiota and its role in regulating intestinal barrier function and a few common pediatric diseases. Disruption in the establishment of a stable normal gut microflora may contribute to the pathogenesis of diseases including inflammatory bowel disease, nosocomial infection, and neonatal necrotizing enterocolitis.

Endovascular recanalization of superior vena cava, brachiocephalic, and subclavian venous occlusions caused by nonmalignant lesions.

BACKGROUND: Endovascular recanalization (EVR) is becoming the primary therapy for patients with central venous (brachiocephalic, subclavian, and superior vena cava) occlusion (CVO) caused by benign etiology. In this study, we retrospectively analyzed our experience in using EVR to treat benign CVO in 10 patients between April 2005 and September 2010. METHODS: The mean age of the patients was 65.3 years, 2/10 cases were female, and the origin of cause of CVO in 7/10 cases was the hemodialysis access in the upper extremity. The patients were treated with primary stent placement and evaluated with immediate technical success rate and post-interventional patency rate after the procedure. RESULTS: Eight patients were treated successfully with stent placement and experienced symptomatic relief immediately. No technical complications were observed during EVR treatment. Patients were followed up by ultrasonography and venography. Median follow-up was 13 months. Three patients required secondary procedures to maintain patency. CONCLUSIONS: EVR is an effective and safe treatment in patients with benign CVO. It provides immediate symptom relief and maintains a continuous access for hemodialysis.

[Subintimal arterial flossing with antegrade-retrograde intervention technique to treat long-segment occlusion of peripheral artery].

OBJECTIVE: To discuss the technique details of subintimal arterial flossing with antegrade-retrograde intervention (SAFARI) to improve technical success in the treatment of chronic total occlusions (CTO) diseases in lower extremity when there is failure to reenter the distal true lumen. METHODS: Between May 2009 and Aug 2010, 15 patients underwent endovascular recanalization with SAFARI technique. There were 8 male and 7 female patients with a mean age of 74.9 years. There were 3 patients with severe claudication (Rutherford category 3) and 12 patients with critical limb ischemia (Rutherford category 4 to 6). The clinical and follow-up data of these patients were analyzed retrospectively. RESULTS: Fourteen patients were treated with SAFARI technique successfully. The technique success rates were 93.3%. The mean ankle brachial index increased from 0.39 to 0.83.Symptoms were relieved in 86.6% patients, Ulcer were healed in 93.3%patients. CONCLUSIONS: SAFARI technique is a safe and effective method in treating CTO diseases, when it is failure to renter the distal true lumen with subintimal angioplasty technique.

Improved liquid chromatography-tandem mass spectrometry method for the analysis of eptifibatide in human plasma.

A rapid, selective and highly sensitive high performance liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of eptifibatide in human plasma. Eptifibatide and the internal standard (IS), EPM-05, were extracted from plasma samples using solid phase extraction. Chromatographic separation was performed on a C(18) column at a flow rate of 0.5 mL/min. Detection of eptifibatide and the IS was achieved by tandem mass spectrometry with an electrospray ionization (ESI) interface in positive ion mode. Traditional multiple reaction monitoring (MRM) using the transition of m/z 832.6-->m/z 646.4 and m/z 931.6-->m/z 159.4 was performed to quantify eptifibatide and the IS, respectively. The calibration curves were linear over the range of 1-1000 ng/mL with the lower limit of quantitation validated at 1 ng/mL. The intra- and inter-day precisions were within 13.3%, while the accuracy was within +/-7.6% of nominal values. The validated LC-MS/MS method was successfully applied for the evaluation of pharmacokinetic parameters of eptifibatide after intravenous (i.v.) administration of a 45 microg/kg bolus of eptifibatide to 8 healthy volunteers.

Drug packaging and delivery using perfluorocarbon nanoparticles for targeted inhibition of vascular smooth muscle cells.

AIM: To investigate the in vitro release profile of drugs encapsulated within perfluorocarbon (PFC) nanoparticles (NPs) and their ability to inhibit the activity of vascular smooth muscle cells (SMCs). METHODS: Dexamethasone phosphate (DxP) or dexamethasone acetate (DxA) was encapsulated into PFC nanoparticles using a high-pressure homogenous method. The morphology and size of the NPs were examined using scanning electron microscopy (SEM) and a laser particle size analyzer. Drug loading and in vitro release were assessed by high-performance liquid chromatography (HPLC). The impact of NP capsules on SMC proliferation, migration and apoptosis in vitro was assessed using cell counting kit-8, transwell cell migration and flow cytometry assays. RESULTS: The sizes of DxP-NPs and DxA-NPs were 224+/-6 nm and 236+/-9 nm, respectively. The encapsulation efficiency (EE) of DxP-NPs was 66.4%+/-1.0%, with an initial release rate of 77.2%, whereas the EE of DxA-NPs was 95.3%+/-1.3%, with an initial release rate of 23.6%. Both of the NP-coated drugs could be released over 7 d. Human umbilical artery SMCs were harvested and cultured for four to six passages. Compared to free DxP, SMCs treated with tissue factor (TF)-directed DxP-NPs showed significant differences in the inhibition of proliferation, migration and apoptosis (P<0.05). CONCLUSION: The results collectively suggest that PFC nanoparticles will be beneficial for targeted drug delivery because of the sustained drug release and effective inhibition of SMC proliferation and migration.

[Effect of adenoviral vectors on the differentiation potential of human bone marrow mesenchymal stem cells].

OBJECTIVE: To investigate the effect of adenoviral vector infection on the differentiation potential of human bone marrow mesenchymal stem cells (hMSCs). METHODS: The third-passage hMSCs were infected with the recombinant adenovirus expressing green fluorescence protein (GFP) for 2, 4, 8 and 16 days. RT-PCR was used to detect the mRNA expression of endodermal marker CYP 51, mesodermal marker SM22alpha, ectodermal marker nestin, pluripotent marker oct-4 and the alternative splicing factor nPTB. Seven days after adenovirus infection, the hMSCs were cultured in the presence of adipogenic agents for 14 days, and the adipose cells differentiated from hMSCs were detected with oil red O staining. RESULTS: Compared with normal hMSCs, the cell infected with the adenovirus for 2, 4, 8 and 16 days showed no obvious down-regulation of CYP51, SM22alpha, nestin, OCT4 or nPTB. The hMSCs 7 days after adenovirus infection were induced to differentiate into adipose cells, with a similar differentiation rate to that of normal hMSCs. CONCLUSION The differentiation potential of hMSCs is not affected by adenovirus infection, suggesting that adenovirus can be used as the gene delivery vector in MSC differentiation studies.

Rapid and sensitive HPLC-MS/MS method for pharmacokinetic assessment of ribavirin in healthy Chinese.

A rapid and sensitive quantitative assay method was developed for determining ribavirin pharmacokinetic in human plasma. The chromatographic separation was achieved within 4.5 min using a SinoChrom ODS-BP column (4.6 x 150 mm, 5 microm) with acetonitrile-water (1 mmol/L ammonium acetate buffer, 0.1% formic acid; 15:85, v/v) at a constant flow rate of 0.8 mL/min. The MRM pairs were m/z 245.2 --> m/z 113.1 for ribavirin and m/z 226.1 --> m/z 152.1 for acyclovir (internal standard), respectively, with dwell times of 200 ms for each transition. The results showed calibration curve for ribavirin was linear over a concentration range of 1-1000 ng/mL. The lower limit of quantification (LLOQ) was 1 ng/mL ribavirin. Twenty healthy volunteers received a 300 mg oral dose of ribavirin. Blood samples were then collected up to 120 h postdosing. All plasma data were comodeled for ribavirin by using noncompartmental modeling. The single dose of ribavirin was well tolerated and no serious adverse effects occurred. The mean time to maximum concentration was about 1.25 h. The mean maximum concentration of drug in plasma for oral ribavirin was 250 ng/mL. The mean elimination half-life was 43.6 h. The present study describes a simple, specific, sensitive HPLC-MS/MS method for measuring plasma drug concentration and analyzing human pharmacokinetics of ribavirin.