PTX Group Research Articles

Effects of parathyroidectomy versus observation on the development of vertebral fractures in mild primary hyperparathyroidism.

Mild primary hyperparathyroidism (PHPT) is a common disease especially in middle-aged and elderly women. The diagnosis is frequently made incidentally and treatment strategies are widely discussed. To study the effect of parathyroidectomy (PTX) compared with observation (OBS) on biochemistry, safety, bone mineral density (BMD), and new fractures. Prospective, randomized controlled study (SIPH study), with a 5-year follow-up. The study was conducted at multicenter, tertiary referral centers. Of 191 randomized patients with mild PHPT, biochemical data were available for 145 patients after 5 years, with a mean age at inclusion of 62.8 years (OBS group, 9 males) and 62.1 years (PTX group, 10 males). Parathyroidectomy vs observation. Biochemistry, BMD, and new radiographic vertebral fractures. Serum-calcium and PTH-levels normalized after surgery and did not deteriorate by observation. BMD Z-scores were normal at inclusion in the lumbar spine (LS) and femoral neck (FN). For LS, BMD Z-scores were stable for 5 years with observation, but decreased in FN (P < .02). After surgery, BMD Z-scores increased significantly in both compartments (P < .02 for both), with a highly significant treatment effect of surgery compared to observation (P < .001). During follow-up, five new clinically unrecognized vertebral fractures were found in 5 females, all in the OBS group (P = .058). Even though new vertebral fractures occurred only in the observation group, the frequency was not significantly different from the surgery group. Longer follow-up is needed before firm conclusions can be drawn about the long-term safety of observation, as opposed to surgery.

Tailored polymer–lipid hybrid nanoparticles for the delivery of drug conjugate: Dual strategy for brain targeting

The object of the present study was to investigate the glioma targeting propensity of folic acid (F) decorated polymer–lipid hybrid nanoparticles (PLNs) encapsulating cyclo-[Arg-Gly-Asp-d-Phe-Lys] (cRGDfK) modified paclitaxel (PtxR-FPLNs). The prepared PLNs were supposed to bypass the blood–brain barrier (BBB) efficiently and subsequently target integrin rich glioma cells. The developed formulations were characterized for size, shape, drug entrapment efficiency, and in vitro release profile. PtxR-FPLNs demonstrated highest in vitro inhibitory effect, cell apoptosis and cell uptake. Pharmacokinetics and biodistribution studies showed efficacy of PtxR-FPLNs in vivo. In vivo anti-tumor studies clearly revealed that the median survival time for Balb/C mice treated with PtxR-FPLNs (42 days) was extended significantly as compared to PtxR-PLNs (35 days), free PtxR (18 days), Ptx-FPLNs (38 days), Ptx-PLNs (30 days), free Ptx (14 days) and control group (12 days). From the results it can be concluded that the developed dual targeted nanoformulation was able to efficiently cross the BBB and significantly deliver higher amounts of drug to brain tumor for better therapeutic outcome.

Bu-zhong-yi-qi pill alleviate the chemotherapy-related fatigue in 4 T1 murine breast cancer model.

BackgroundPaclitaxel induced fatigue still remains underrecognized and undertreated, partly because of limited understanding of its pathophysiology and lack of effective treatments. This study is aim to evaluate the anti-fatigue effects and mechanism of Bu-Zhong-Yi-Qi pill in murine 4 T1 breast cancer mice were treated with paclitaxel.MethodsBreast cancer mice established with murine 4 T1 cells were randomly and repectively divided into five groups: negative control group (NC), tumor control group (TC), paclitaxel group (PTX), Bu-Zhong-Yi-Qi pill group (BZYQ) and Bu-Zhong-Yi-Qi pill plus paclitaxel group (BZYQ + PTX). The mice were administered for 21 days. During this period, the tumor volume, body weight and the weight-loaded swimming time were measured. After the last administration, all mice were sacrificed, weighted the tumor, measured immune cell cytokines and oxidative stress indicator. The remaining 10 mice in each group were observed for survival analysis.ResultsTreatments with BZYQ + PTX and PTX significantly reduced the rates of tumor volume in comparison with TC starting on the 9th day and the 18th day respectively (P < 0.05-0.01), and presented decreased tumor weight compared to TC (P < 0.05-0.01). Compared with mice in TC group, the median survival time and the average survival time in BZYQ + PTX group, BZYQ group and PTX group were significantly prolonged (P < 0.05-0.01). The swimming time of the BZYQ + PTX group gradually increased, which is longer than the PTX group on Day 14 and Day 21 (P < 0.01). The level of TNF-α was lower in BZYQ + PTX group than PTX group (P < 0.01). The level of SOD activity in BZYQ + PTX group was lower than the NC group (P <0.01), but much higher than the PTX group (P < 0.01). The level of MDA of BZYQ + PTX group was higher than the NC group (P < 0.01), but significant lower than the PTX group (P < 0.01).ConclusionsBZYQ has the potential of alleviating paclitaxel chemotherapy-related fatigue in 4 T1 breast cancer mice by reducing the serum levels of TNF-α and modulating the level of MDA and the SOD activity.

Development of hypoparathyroidism animal model and the feasibility of small intestinal submucosa application on the parathyroid autotransplantation.

The purpose of this study is to evaluate the feasibility of small intestinal submucosa (SIS) application on the parathyroid autotransplantation in a rat model of hypoparathyroidism. The rats were divided into four groups: NC (no procedure, n = 5), PTX (total parathyroidectomy, n = 6), PT (total parathyroidectomy and parathyroid autotransplantation, n = 10) and PT + SIS group (total parathyroidectomy and parathyroid autotransplantation with SIS, n = 10). The levels of parathyroid hormone (PTH), calcium, and phosphorous were measured on 0, 3, 7, 21, 56 and 84 days after surgery. PTH level was expressed as median (interquartile range) and histological and immunohistochemical examinations were performed. PTH levels were significantly decreased to "not detectable level" from day 3 in PTX group. PTH was not detected in both PT and PT + SIS groups on the 21st day. On the 56th day, PTH levels were increased in both groups: 3 out of 8 rats (37.5%) in the PT group, 6 out of 9 rats (66.7%) in the PT + SIS group. The PTH level was fully recovered to its preoperative range on the day 84 as 6 of 8 rats (75%) of the PT group and 7 of 9 rats (77.8%) of the PT + SIS group were recovered; the PTH levels were 117.84 and 178.36 pg/ml, respectively. The neo-vascularization was well observed around the parathyroid tissue, and the number of new vessels formed was higher in the PT + SIS group (15 vessels/high power field) as compared to the PT group (10 vessels/high power field). This study showed the feasibility and the treatment effect of SIS as the success rate of autotransplantation of parathyroid tissue was significantly increased without severe inflammatory response in hypothyroidism animal model.

Histological modification in TRAM flap in rats treated with pentoxifylline.

To investigate the blood vessels' concentration in TRAM flap's rat model, in the presence of pentoxifylline. 32 male, Wistar-EPM rats were divided into two groups. Control group (C): 0.5 ml of saline, intraperitoneally, once a day, for seven days before flap elevation; PTX group (P): pentoxifylline (20mg/kg/day), intraperitoneally, for seven days before flap elevation. After that, they were submitted to a caudal unipedicle TRAM flap. On the fifth postoperative day, percentages of flap necrosis were determined via the "paper template" method and Tram flap's zone IV skin biopsies were taken for histological analysis. the mean percentage of flap necrosis in group C was 58.7 % and in group P, 31.1 (Wilcoxon test; p = 0.003). Mean capillary vessels number in zone IV's skin in C group was 33.4 and in P group was 71.9 (p=0.008). Pentoxifylline was effective reducing the necrosis in the caudal unipedicle TRAM flap in the rat as well as increasing the number of capillaries in an ischemic zone (zone IV).

Pentoxifylline During Steroid Window At Induction To Remission Increases Apoptosis In Childhood Acute Lymphoblastic Leukemia

IntroductionAcute lymphoblastic leukemia (ALL) is the most common cancer diagnostic in children, and it represents the second death cause in this population. Despite advances in the treatment of childhood ALL, there are small portion of patients whom still succumb to this disease.A reduced apoptosis in cells plays an important role in carcinogenesis. This phenomenon is an important component in the cytotoxicity induced by anticancer drugs. A currently challenge is the chemotherapy resistance of tumor cells, inhibiting the apoptosis induced by chemotherapy.Pentoxifylline, (PTX) has been studied for its role on increase of apoptosis on cancer cells by different pathways. Our group has reported its efficacy in vitro and ex vivo in increasing apoptosis induced by chemotherapy drugs such as adriamycin and cisplatin in fresh leukemic human cells, lymphoma murine models and cervical cancer cells. We conducted a phase 1 controlled randomized trial to evaluate the efficacy of adding PTX to the steroid window during the remission induction phase in new diagnosed children with ALL. MethodsWe included all children from both sexes from 9 months to 17 years old during October 2011 to December 2012. Patients were divided into 3 groups, the first one as a non-malignant control group (NL group) included children with a non-hematology disease in which bone marrow aspiration (BMA) was mandatory in order to reach the diagnosis. The second one, the ALL control group whom received prednisone (PRD group) for the steroid window at 40mg/m2/day PO from day -7 to day 0; and then the third one (PTX group), the study group which included children receiving the steroid phase with PRD as early described, plus PTX at 10mg/kg/day IV divided in 3 doses, at the same days as recommended in our treatment protocol (Total Therapy XV). For all 3 groups a BMA was performed at diagnosis, for PRD group as well as PTX group, a second BMA was also collected at day 0. Apoptosis was evaluated by means of Annexin V Apoptosis Detection Kit FITC/PI (eBioscience¨, San Diego, CA, USA) in 1×106 bone marrow mononuclear cells. We measured minimal residual disease (MRD) by flow cytometry at day 14 to demonstrate complete remission in leukemic patients. Statically analysis was performed by U Man Whitney. ResultsWe enrolled 32 patients: 10 in NL group; 11 in PRD group; and 11 in PTX group. The median age of all groups was 6 years (range 9 months-17 years). In PRD group, patient 1 abandoned treatment after administration of day 0, nevertheless the second BMA sample was collected. Patient number 7 died at day 4 due to complications from tumor lysis syndrome. Consequently, in these patients we were not able to measure MRD and BM aspiration at day 14. Except one patient in PRD group, all achieved complete remission at day 14. We did not find any significant difference between NL group and PRD and PTX groups before intervention (U=32 p=0.7; U=28.5 p=0.48 respectively). There was no significant difference between treatment groups before intervention (U= 37 p=0.79). However, after treatment we found an important difference between PRD and PTX groups, we observed an increase in apoptosis in PTX group in comparison with PRD group (U=17.5 p=0.04). There were no adverse effects during treatment. ConclusionsThe present study is the first one that shows the efficacy of PTX in increasing apoptosis induced by PRD in new ALL diagnosed children, whom have not received any treatment yet. This might be helpful, not only in patients with relapse, but to increase the overall cure rate in ALL. Further studies are needed to prove this hypothesis. With this objective, our study group is already planning a second trial were PTX will be given during all remission induction phase. Experimental reports strongly suggest that PTX induces inhibition of the transcription factor NF-ĸB, by inhibiting survival gens and facilitating apoptosis. To prove it, we are currently processing these patients' samples to know their genetic expression. Disclosures:No relevant conflicts of interest to declare.

Effects of Dietary Phosphate on Adynamic Bone Disease in Rats with Chronic Kidney Disease – Role of Sclerostin?

High phosphate intake is known to aggravate renal osteodystrophy along various pathogenetic pathways. Recent studies have raised the possibility that dysregulation of the osteocyte Wnt/β-catenin signaling pathway is also involved in chronic kidney disease (CKD)-related bone disease. We investigated the role of dietary phosphate and its possible interaction with this pathway in an experimental model of adynamic bone disease (ABD) in association with CKD and hypoparathyroidism. Partial nephrectomy (Nx) and total parathyroidectomy (PTx) were performed in male Wistar rats. Control rats with normal kidney and parathyroid function underwent sham operations. Rats were divided into three groups and underwent pair-feeding for 8 weeks with diets containing either 0.6% or 1.2% phosphate: sham 0.6%, Nx+PTx 0.6%, and Nx+PTx 1.2%. In the two Nx+PTx groups, serum creatinine increased and blood ionized calcium decreased compared with sham control group. They also presented hyperphosphatemia and reduced serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels. Fractional urinary excretion of phosphate increased in Nx+PTx 1.2% rats despite lower PTH and FGF23 levels than in sham group. These biochemical changes were accompanied by a decrease in bone formation rates. The Nx+PTx 1.2% group had lower bone volume (BV/TV), higher osteoblast and osteocyte apoptosis, and higher SOST and Dickkopf-1 gene expression than the Nx+PTx 0.6% group. Nx+PTx 0.6% rat had very low serum sclerostin levels, and Nx+PTx 1.2% had intermediate sclerostin levels compared with sham group. Finally, there was a negative correlation between BV/TV and serum sclerostin. These results suggest that high dietary phosphate intake decreases bone volume in an experimental model of CKD-ABD, possibly via changes in SOST expression through a PTH-independent mechanism. These findings could have relevance for the clinical setting of CKD-ABD in patients who low turnover bone disease might be attenuated by optimal control of phosphate intake and/or absorption.

Parathyroidectomy improves cardiovascular outcome in nondiabetic dialysis patients with secondary hyperparathyroidism

Secondary hyperparathyroidism and its associated abnormalities in mineral metabolism and haemodynamic changes increase the cardiovascular risk in patients with end-stage renal disease (ESRD). Our objective was to determine the association of parathyroidectomy (PTX) with major cardiovascular events in nondiabetic dialysis patients with severe secondary hyperparathyroidism (SHPTH). We performed a cohort study with fifty-three nondiabetic ESRD patients who were treated with maintenance haemodialysis and who had intact parathyroid hormone (PTH) levels > 800 pg/ml. Participants received either only medical therapy or medical therapy and total PTX with autotransplantation for SHPTH. We evaluated the associations between PTX and major cardiovascular events including death, cerebrovascular accident and myocardial infarction. The biochemical and haemodynamic changes associated with PTX were measured. During the mean follow-up of 72 months, twenty-three patients received only medical treatment (medical group) while thirty patients underwent PTX in addition to medical treatment (PTX group). The two groups were comparable in respect of baseline characteristics. PTX group was found to be associated with a reduced incidence of major cardiovascular events (P = 0·021). A multiple Cox regression analysis showed that the variable significantly associated with major cardiovascular events was treatment modality (medical therapy vs medical therapy and parathyroidectomy, hazard ratio = 26·12, 95% CI = 1·30-526·27, P = 0·033). Blood pressure, haemoglobin, alkaline phosphatase, calcium, phosphate and calcium × phosphate product significantly improved after PTX. PTX was associated with better cardiovascular outcome in nondiabetic dialysis patients with severe SHPTH.

Parathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidism, as evaluated by exercise test

To investigate whether parathyroidectomy (PTx) reverses risk factors for arrhythmias related to the QT dynamic changes evaluated during bicycle ergometry exercise test (ET). Twenty-four postmenopausal women with primary hyperparathyroidism (PHPT) (mean age 60.08.4 years) and 30 sex- and age-matched controls underwent ET, echocardiography, and biochemical evaluation. The following stages were considered during ET: rest, peak exercise, and recovery. The patients were randomized to two groups: 12 underwent PTx (group A) and 12 were followed-up conservatively (group B). After 6 months, the patients were studied again. Groups A and B showed no differences in mean baseline biochemical values, echocardiographic parameters, and QTC interval. PHPT patients showed an increased occurrence of ventricular premature beats (VPBS) during ET compared with controls (37.0 vs 6.6%, P=0.03). Serum calcium level was a predictor of VPBS (P=0.05). Mean value of QTC was in the normal range at baseline (Group A: 401±16.9; group B: 402.25±13.5 ms) but significantly lower than controls (417.8±25.1 ms, P<0.01). A negative correlation was found between QTc and calcium values (P=0.03). Physiological reduction of QTc interval from rest to peak exercise was not observed in PHPT patients before surgery. After PTx, group A had a significant reduction in VPBs compared with baseline (at baseline, 5 of 12 vs none of 12 patients after PTx, P=0.03) and a restored normal QT adaptation during ET. Group B showed no significant changes after a 6-month period. PTx reduces the occurrence of VPBs and restored the QTc adaptation during ET.

Experimental Model of Degloving Injury in Rats

Degloving injuries may be a challenge when it comes to deciding the surgical approach to be used. Repositioning of the flap and suturing are faster and more straightforward, but often these procedures often lead to total or partial loss of the avulsed flap. Pharmacological agents with vascular properties that enhance the viability of the reattached flap could be beneficial to patients with degloving injuries. Experimental models with which to test this hypothesis are scarce. An experimental model reproducing a degloving injury of the hind limb of rats was developed in our department, and the effects of pentoxifylline (Ptx) and allopurinol (Alp) were assessed. In all, 3 groups of rats were studied (25 rats each). A hind limb degloving model was used in all groups, resulting in a reverse flow flap. The flap was then repositioned and sutured. The control (Ct) group received only saline solution, the Ptx group received pentoxifylline (25 mg/kg), and the Alp group received allopurinol (45 mg/kg). The rats were observed for 7 days, after which they were killed, and the flap was removed. The total area of the avulsed flap and the necrotic area were measured. The median total flap area (cm) was 5.6 for the Ct group, 5.5 for the Ptx group, and 5.8 for the Alp group (P = 0.9465). Thus, the flaps were similar. The median necrotic flap area (cm) was 3.3 for the Ct group, 2.3 for the Ptx group, and 1.9 for the Alp group (P = 0.0001). There was a statistical difference between the Ct and Ptx groups and the Ct and Alp groups (P < 0.05). The areas of necrosis observed in the degloved flaps of the rats' hind limbs were smaller in the pentoxifylline and allopurinol groups. Although allopurinol seems to be more efficient, the difference was not significant.

Inflammatory and apoptotic alterations in serum and injured tissue after experimental polytrauma in mice

The exact alterations of the immune system after polytrauma leading to sepsis and multiple-organ failure are poorly understood. Thus, the early local and systemic inflammatory and apoptotic response was characterized in a new polytrauma model and compared with the alterations seen after single or combined injuries. Anesthetized C57BL/6 mice were subjected to either blunt bilateral chest trauma (Tx), closed head injury, right femur fracture including contralateral soft tissue injury, or a combination of injuries (PTx). After 2 hours or 6 hours, animals were sacrificed, and the systemic as well as the local pulmonary immune response (bronchoalveolar lavage [BAL]/plasma cytokines, lung myeloperoxidase [MPO] activity, and alveolocapillary barrier dysfunction) were evaluated along with lung/brain apoptosis (lung caspase 3 Western blotting, immunohistochemistry, and polymorphonuclear leukocytes [PMN] Annexin V). Hemoglobin, PO2 saturation, and pH did not differ between the experimental groups. Local BAL cytokines/chemokines were significantly increased in almost all groups, which included Tx. There was no further enhancement of this local inflammatory response in the lungs in case of PTx. At 2 hours, all groups except sham and closed head injury alone revealed an increased activity of lung MPO. However, 6 hours after injury, lung MPO remained increased only in the PTx group. Increased BAL protein levels were found, reflecting enhanced lung leakage in all groups with Tx 6 hours after trauma. Only after PTx was neutrophil apoptosis significantly decreased, whereas lung caspase 3 and plasma interleukin 6/keratinocyte chemoattractant (KC) were substantially increased. The combination of different injuries leads to an earlier systemic inflammatory response when compared with the single insults. Interestingly, only after PTx but not after single or double hits was lung apoptosis increased, and PMN apoptosis was decreased along with a prolonged presence of neutrophils in the lungs, which may therefore represent a possible pathomechanism for lung injury after polytrauma.

Tertiary Hyperparathyroidism in Kidney Transplant Recipients

Several treatment options exist for kidney transplant patients with tertiary hyperparathyroidism. However, the decision to endorse observation (OBS), medical therapy, or parathyroidectomy (PTX) remains controversial. We performed a retrospective cohort study of kidney transplant patients with tertiary hyperparathyroidism at a single institution over a 7-year period. Patients were classified by treatment mode: OBS, medical therapy with cinacalcet (CIN), or PTX. Descriptive statistics were performed. Serum calcium levels and change in serum creatinine level were compared using analysis of variance with comparisons between individual groups using the Student's t test with a Bonferroni correction. Time to treatment was compared between CIN and PTX groups using the Student's t test. Complication rates were compared using the Fisher exact test. We identified 83 patients: 52 were treated by OBS; 13 were treated with CIN, and 18 underwent PTX. Six weeks after treatment, PTX resulted in lower serum calcium level (9.28 mg/dL) compared with CIN (10.20 mg/dL) (P<0.01). There was no difference in the change in serum creatinine level 1 year after treatment initiation (P=0.98). Time to treatment was shorter (1.7 vs. 3.3 years, P<0.01), and the highest pretreatment calcium level was higher (12.2 vs. 11.7 mg/dL, P<0.01) in patients treated with PTX compared with CIN. Complication rates differed by treatment group (P<0.01). A quarter of OBS patients showed persistent hypercalcemic symptoms, compared with only 7.7% in the CIN group and 0% in the PTX group (P<0.01). PTX led to a greater reduction in serum calcium level and lower chance of persistent hypercalcemic symptoms, without any appreciable harm to the kidney allograft.

The treatment of secondary hyperparathyroidism in haemodialysis patients' refractory to alfacalcidol

Background. Secondary hyperparathyroidism (sHPT) is one of the serious complications in chronic kidney disease and is associated with progressive bone disease and vascular calcification.The objective of the study was to determine the impact of Mimpara (Cinacalcet HCl) on mineral disorder, bone turnover and bone mineral density (BMD) versus parathyroidectomy (PTx) in haemodialysis patients’ refractory to alfacalcidol. Materials and methods. 62 haemodialysis patients with sHPT were enrolled in this 6=months prospective study. All of them had surgical indications for PTx. Surgical indications was established according to clinical or biological assessment. 40 patients underwent Mimpara treatment. Dose of Mimpara was titrated every 4 weeks. Sequential doses included 30–180 (mean 59.1 ± 34.2) mg/day. 22 patients underwent PTx. The surgical technique was depended on quantity of hyperplastic parathyroid glands.Results. In 6 months mean iPTH, Ca, Са×Р, CTx and OC levels significantly decreased by 55.7%, 13.8%,34.3%, 21.4 and 1.4% in the Mimpara group vs. 90.7%, 14%, 55.5%, 58.7% and 26.9% in the PTx group. Median serum iPTH level decreased by 30% after initiation of Mimpara in 94.3% patients, from them by 50%in 74.3%. Achieved the KDOQI treatment targets for PTH in 28.6% patients.In 6 months after PTx median serum iPTH level was &lt;100 pg/ml in 50% patients, achieved the KDOQI treatment targets in 27.3%, &lt;300 pg/ml in 18.2%. Median serum 25(ОН)D after PTx significantly increase by 127.3% vs 6.72% in the Mimpara group. In 6 months active restoration of BMD was found in the PTx patients, and patients treated with Cinacalcet showed stabilization of BMD.Mimpara therapy led to a reduction in glandular volume during the course of the study: in both glands with a baseline volume &lt;500 mm3 and with a baseline volume ≥500 mm3. Conclusions. PTx and Cinacalcet therapy improves phosphorus=calcium homeostasis, bone turnover, but bone resorption and formation markers decreased better in the PTx group compared to Cinacalcet group. The effectiveness and safety of Mimpara for secondary hyperparathyroidism were evaluated in dialysis patients’ refractory to alfacalcidol, which reduced the need for parathyroidectomy in patient without severe osteodystrophy.

The effect of pentoxifylline on reduction of proteinuria among patients with type 2 diabetes under blockade of angiotensin system: a double blind and randomized clinical trial.

Although blockade of renin-angiotensin system have been cited as the first line of therapy for the management of diabetic nephropathy (DN), however in a substantial number of patients, progression of renal disease are not completely halted by these agents. We have conducted a double blinded clinical trial to assess the additive effect of pentoxifylline on reduction of proteinuria among patients with type 2 DM under blockade of angiotensin system. The dosage of PTX used in our trial was at a low dosage of 400mg daily and to our knowledge, we did not found article which evaluated the antiproteinuric effect of pentoxifylline in this dosage. One hundred patients with DN and persistent proteinuria despite treatment with losartan and enalapril in at least 3 months before inclusion in the study were randomly assigned to two groups. Control group (n=50, 26 males and 24 females) received losartan and enalapril, while treatment group (PTX Group) (n=50, 28 males and 22 females) was given losartan, enalapril and pentoxifylline 400mg/day for 6 months. At the beginning of the study there were no significant differences in demographic and clinical characteristics of patients including serum creatinine, HbA1c, blood pressure and urinary protein excretion between two groups (P&gt;.05). In the PTX group, the mean rate of urinary protein excretion have significantly decreased from 616.66mg to 378.24 after 3 months (P=.000) and to 192.05mg after 6 months (P=.000) whereas no significant changes were observed in the control group. The beneficial antiproteinuric effect of PTX was not associated to the degree of metabolic control and a reduction of blood pressure. In addition, at the end of study, the mean clearance of creatinine was significantly higher in PTX group (P=.04). In conclusion, PTX can significantly provide additive antiproteinuric effect and slow the decrease in GFR among patients with type 2 DM under blockade of angiotensin system.

Late breaking clinical trials 1

Background: The Zilver® PTX® stent with polymer-free paclitaxel coating is the first drug-eluting stent approved (currently CE marked, investigational in the United States and Japan) for the superficial femoral artery (SFA). This multicenter, multinational, prospective, randomized trial compared the safety and effectiveness of the Zilver PTX study to balloon angioplasty (PTA) and bare metal stenting (BMS). Methods: Symptomatic patients with SFA lesions (de novo or non-instent restenosis) were randomized to PTA or Zilver PTX stent placement. PTA patients experiencing acute failure (e.g. 30% residual stenosis) underwent secondary randomization to provisional stenting with Zilver BMS or Zilver PTX. Follow-up included event-free survival (EFS), and primary patency by Duplex ultrasound core laboratory analysis (peak systolic velocity ratio 2.0). Results: 479 patients were enrolled at 55 institutions in the United States, Japan and Germany, with 241 patients randomized to the Zilver PTX group and 238 to the PTA group. Demographics and lesion characteristics (e.g., lesion length 66 mm and 63 mm, respectively) were similar for the groups. Approximately half the PTA group experienced acute failure and underwent secondary randomization; 59 and 61 patients were assigned to provisional stenting with Zilver BMS and Zilver PTX, respectively. The study results met the 12-month primary endpoint goals showing non-inferior EFS (90.4% versus 82.6%, p 0.01) and superior primary patency (83.1% and 32.8%, p 0.01) for the Zilver PTX compared to PTA. The randomized comparison of provisional stenting with Zilver PTX versus Zilver BMS also showed significant paclitaxel coating benefit, with 12-month patency rates of 89.9% and 73.0% respectively (p 0.01). Currently, 24-month follow-up is available for 278 patients, showing an 86.6% EFS rate and a 74.8% patency rate. The randomized comparison of provisional stenting with Zilver PTX versus Zilver BMS continues to demonstrate significant paclitaxel coating benefit at 24 months, with patency rates of 81.2% and 62.7% respectively (p 0.01). Conclusion: The results of this randomized, multicenter study support the safety and effectiveness of the Zilver PTX Drug-Eluting Peripheral Stent.

Effect of pentoxiflline on the spinal cord glial cells activation in a rat model of postoperative pain

Objective To investigate the effect of intraperitoneal administration of pentoxifylline on the development of hyperalgesia and the activation of glial cells in a rat model of postoperative pain. Methods Sixty male SD rats weight 190 g-220 g were randomly divided into 2 groups: control group (NS group) and treatment group (PTX group), in which 50 mg/kg saline vehicle or pentoxifylline (n=30) was given intraperitoneally 15 min before surgery and continued once a day to the 5th day after the operation, respectively.The animal model of postoperative pain was established by incision hind paw. Cumulative pain score and paw withdrawal threshold were measured at 1 d before operation and then at 1, 2, 3, and 5 h and 1, 2, 3, and 5 d after operation.Spinal cord tissue samples from rats were taken for analysis of glial fibrillary acid protein (GFAP) and ionized calcium bindingadaptor molecule-1 (Iba-1) expression by means of immunohistochemistry at the following times after operation: 1, 2, 3, and 0.8, 6.6±0.5, 8.6±0.7, 10.2±0.4, 7.0±0.6 and 5.6±0.5 in the PTX group respectively, less than the NS group with 4.0±0.6, 6.0±and 3 d, the PWT were (5.8±1.6), (5.2±1.1), (4.4±0.6), (4.9±0.4), (5.2±1.1), (7.6±1.8) and (10.4±1.6) g in the PTX group respectively, more than the NS group with (2.4 ±0.8), (2.1±0.5), (2.0±0.5), (2.1±0.3), (2.3±0.5), (4.5±0.9)and(8.1±1.4) g 205.6±4.2 and 230.2±3.2 in the PTX group respectively, lower than the NS group with 244.1±4.9, 258.6±4.12 and 276.2±3.4 (P＜the PTX group respectively, lower than the NS group with 230±3 and 205±4 (P＜0.05). Conclusion Pentoxifylline can attenuate the process of mechanical allodynia in a rat model of postoperative pain, its main mechanism may be related to the inhibition of glial cells activation in the spinal cord. Key words: Pentoxifylline; Postoperative pain; Astrocyte; Microglia

619 Long Term Outcomes after Lung Transplantation in Eisenmenger's Syndrome Compared with Idiopathic Pulmonary Arterial Hypertension

patients. Results: 78 patients were in the PTx group and 10 patients were in the RTx group. PTx differed from RTx in that patients were older 47 10 vs. 37 8 years. They did not differ in sex, race, six minute walk, serum creatinine, bilirubin or functional status. Patient survival during the study interval was not different between PTx and RTx. However, patients retransplanted for BO had an increased rate of BO development in the retransplanted lungs (p 0.03).

Clinical observation of Pentoxifylline combined with mechanical ventilation in acute respiratory distress syndrome

Objective To explorer the clinical effects of Pentoxifylline(PTX group) with mechanical ventilation in patients with acute respiratory distress syndrome(ARDS). Methods 64 patients with ARDS were randomized into a control group(n = 32 ,ARDS conventional treatment) and a PTX group(n = 32 ,PTX 50ml iv bid in addition to the conventional treatment). The patients were closely monitored with their curative effect, blood gas indexes and serum levels of TNF-α and IL-8 after the treatment. Results The PaO_2 and PaO_2/FiO_2 got significantly higher in the PTX group than in the control group on 3d and 7d (P ＜ 0.05). The serum levels of TNF-α and IL-8 and the mortality of ARDS were significantly decreased in the PTX group after the combined with Pentoxifylline (P ＜ 0.05 or P ＜0.01). Conclusion The treatment combined with the Pentoxifylline can effectively improve the Oxygenation and prognosis of ARDS patients by inhibiting the inflammatory responses. Key words: Respiration, artificial; Respiratory distress syndrome, adult; Pentoxifylline

Tertiary hyperparathyroidism: Is less than a subtotal resection ever appropriate? A study of long-term outcomes

Our aim was to examine the outcomes of patients with tertiary hyperparathyroidism (3-HPT) who had limited resection of 1 or 2 parathyroids. We reviewed 140 patients with 3-HPT who underwent parathyroidectomy (PTX) at a single institution. Patients were analyzed according to their operation-limited PTX versus subtotal or total PTX. The limited PTX group consisted of 29 patients who underwent resection of 1 (n = 12) or 2 (n = 17) parathyroids. The other 111 patients had subtotal (n = 104), total (n = 3), and/or reoperative PTX (n = 12). The mean +/- SEM follow-up was 79 +/- 5 months. Eucalcemia was achieved in 94% of the patients. All patients with persistent (n = 2) hypercalcemia underwent subtotal PTX (P = not significant [NS] vs limited PTX). In a logistic regression model, the extent of operation was not associated with the development of recurrent disease. Additionally, the incidence of permanent hypocalcemia was 7% after subtotal or total PTX versus 0% after limited resection (P = NS). Long-term outcomes in patients with 3-HPT appear to be similar after appropriate limited resection of 1 or 2 parathyroid glands compared to subtotal or total PTX. Therefore, a strategy of limited parathyroid resection seems appropriate for patients with 3-HPT when the disease is limited to 1 or 2 glands.

Prospective, randomized, controlled trial of parathyroidectomy versus observation in patients with “asymptomatic” primary hyperparathyroidism

Disruptions in cognitive function have been described in the constellation of symptoms associated with "asymptomatic" primary hyperparathyroidism (PHPT). The aim of this study was to determine the impact of parathyroidectomy (PTX) on brain function and sleep in "asymptomatic" PHPT patients. We conducted a prospective, randomized trial comparing immediate PTX with observation in patients with asymptomatic PHPT. We performed functional magnetic resonance imaging (fMRI) of the brain, sleep assessment, and validated neuropsychological battery at baseline, 6 weeks, and 6 months. Wilcoxon rank-sum and Pearson and Spearman correlations were used. A total of 18 patients were randomized. Subjective sleepiness correlated with worse performance on executive function tests during fMRI at 6 weeks (Pearson, -0.473; P = .047) and 6 months (Pearson, -0.673; P = .002). Total sleep time correlated with PTH levels at both 6 weeks (Pearson, 0.518; P = .048) and 6 months (Pearson, 0.567; P = .018). At 6 weeks, hypersomnolence as measured subjectively was decreased in the PTX group, but increased in those observed (-2.56 vs 2.22; P = .03) This prospective, randomized trial for asymptomatic PHPT patients demonstrated an association of sleep with brain function. Sleep seemed to be an indicator of brain activation in the anterior cingulate gyrus and precentral cortex. Subjective sleepiness was associated with executive function. The results of this pilot study suggest that decreased serum PTH levels correlate with improved sleep and that PTX decreases sleepiness in patients with asymptomatic PHPT.