A stereomorphologic study of bone matrix apposition in HA-implanted cavities observed with SEM,being prepared by a microvascular cast and freeze-fracture method

In order to obtain further understanding of the relationship between hydroxyapatite (HA) with regard to its properties as an implantation bed, dense HA particles were implanted into the tibiae of dogs. Following the healing periods of 2 weeks, 1 month, 2 months, 3 months and 6 months, the specimens were prepared with a combination of a microvascular cast method and a freeze-fracture technique, allowing observations to be made with a scanning electron microscope (SEM). Under SEM, osteogenesis among the HA particles developed in a programmed sequence. The unfolding sequence revealed that the sinusoidal capillaries provided the initial evidence of vascularization preceding new bone formation, with microvessels creeping along the interparticular space among the HA particles. Having established an intimate contact existing between the microvessels, collagen fibres and the HA surface, the HA particles served as a supporting scaffold for the vessels to creep over and to connect with each other to form a vascular network. The way that the collagen fibres attached to the HA particles was either through globular depositions or via directly abutting themselves on to the HA surface. On closer inspection the osteoblasts with extracellular collagen fibrils were observed over the HA surface. By appositional growth, osteoblasts laid down a bone matrix in successive layers, forming a woven bone around the HA particles. As the implantation time increased, bony tissues gradually transformed into mature bone occupying all of the interparticular space. This study successfully revealed the spatial relationship between bone cells, collagen fibres and blood vessels in an osteogenetic sequence among HA particles, as revealed by a microvascular cast and the freeze-fracture method.     

Low-dose thalidomide treatment for advanced hepatocellular carcinoma

OBJECTIVE: To analyze the efficacy of oral thalidomide in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: Sixty-eight patients with unresectable and nonembolizable HCC were consecutively enrolled in a compassionate treatment program of oral thalidomide. Tumor response and treatment-related toxicity were prospectively followed. Thalidomide was given at a starting dose of 200 mg per day. The dose was gradually escalated in 100-mg steps up to 600 mg per day if no limiting toxicities developed. RESULTS: Sixty-three patients were evaluable for response. One complete and 3 partial responses, defined by World Health Organization criteria, were seen, with a response rate of 6.3% (95% CI 0-12.5). The duration of response was 50+, 24.6, 11.6+ and 8.7+ weeks, respectively. All 4 responders had a dramatic decrease in alpha-fetoprotein (alpha-FP) levels. Another 6 of the 42 patients with elevated alpha-FP levels before treatment had a more than 50% decrease in their alpha-FP levels after thalidomide treatment. Totally 10 patients had an objective response to thalidomide. The median overall survival for all of the 68 patients was 18.7 weeks (95% CI 11.8- 25.6) with a 1-year survival rate of 27.6%. The median overall survival of the 10 patients with an objective response to thalidomide was 62.4 weeks (95% CI 31.2-93.6 weeks). All responders responded at a dose equal to or less than 300 mg per day. Toxicities of thalidomide were generally manageable, and only 16, 6, and 0 patients developed grade 2, 3, and 4 toxicities, respectively. CONCLUSION: Low-dose thalidomide is safe and induces unequivocal tumor response in a minority of patients with advanced HCC.     

变频电针配合改良药笔灸法治疗带状疱疹后遗神经痛

目的:观察变频电针配合改良药笔灸法治疗带状疱疹后遗神经痛的临床疗效。方法:将37例带状疱疹后遗神经痛患者随机分为对照组19例,采用口服布洛芬胶囊加维生素B1治疗,治疗组18例,采用变频电针配合改良药笔灸法治疗,比较两组视觉模拟评分(VAS)变化及临床疗效。结果:治疗组带状疱疹后遗神经痛的治疗总有效率达到94.44%(17/18),优于对照组的73.68%(14/19)(P<0.05);两组治疗后VAS评分较治疗前均有改善(P<0.05),但两组治疗后比较差异无统计学意义(P>0.05)。结论:变频电针配合改良药笔灸法能有效缓解带状疱疹后遗神经疼痛。     

Expansion of adipose tissue mesenchymal stromal progenitors in serum-free medium supplemented with virally inactivated allogeneic human platelet lysate

BACKGROUND: Single‐donor or pooled platelet lysates (PL) can substitute for fetal bovine serum (FBS) for mesenchymal stromal cell (MSC) expansion. However, for clinical applications of MSCs, the use of virally inactivated PL would be desirable. Recently, we have developed a solvent/detergent (S/D)‐treated human PL preparation (S/D‐PL) rich in growth factors. The capacity to use this virally inactivated preparation for MSC expansion needs to be evaluated. STUDY DESIGN AND METHODS: Platelet concentrates were treated by S/D (1% tri‐n‐butyl phosphate and 1% Triton X‐45), extracted by oil, purified by C18 hydrophobic interaction chromatography, and sterile filtered. S/D‐PL was compared to FBS as a medium supplement (10% vol/vol) for isolating, maintaining, and expanding adipose tissue–derived MSCs (AT‐MSCs). Cell morphology; proliferation kinetics; immunophenotype; differentiation capacity toward the chondrogenic, osteogenic, and osteogenic lineages; and cytokine antibody array were assessed. RESULTS: AT‐MSCs had a typical spindle morphology and proliferated in S/D‐PL at least as well as in FBS. Immunophenotype at Passage 7 was characteristic of MSCs and similar for both culture conditions. Differentiation capacity into the three lineages was maintained and chondrogenesis was enhanced by S/D‐PL. In a 120 human cytokine antibody array analysis, 73 cytokines were detected in S/D‐PL, including 22 with a concentration higher than in FBS. CONCLUSION: S/D‐PL is an alternative to FBS for AT‐MSC maintenance and expansion, does not compromise the differentiation capacity nor the immunophenotype, and may accelerate chondrogenesis. S/D‐PL protocols for MSC clinical scale‐up may represent a major step toward challenging new use in stem cell therapies.     

Human platelet concentrates: a source of solvent/detergent-treated highly enriched brain-derived neurotrophic factor

BACKGROUND: Human blood platelets (PLTs) contain brain‐derived neurotrophic factor (BDNF), a neurotrophin that binds to neurotrophic tropomyosin‐related kinase B (TrkB) receptor on central nervous system cells. This binding promotes neural synaptic plasticity and memory and prevents neuronal degeneration. Alterations in BDNF homeostasis are associated with aging and are found in several neurodegenerative conditions such as Alzheimer's, Huntington's, and Parkinson's diseases and multiple sclerosis. We have developed PLT viral inactivation and chromatographic fractionation processes and decided here to identify fractions enriched in BDNF. STUDY DESIGN AND METHODS: PLT concentrates (PCs) were treated by solvent/detergent (S/D), extracted by oil, and subjected to fractionation (C18, sulfopropyl [SP]‐Sepharose, diethylaminoethyl [DEAE]‐Sepharose, or activated charcoal). BDNF and pro‐BDNF were evaluated by enzyme‐linked immunosorbent assay, and Western blot. TrkB was studied by Western blot. Tri‐n‐butyl phosphate (TnBP) was quantified by high‐performance liquid chromatography, and Triton X‐45 by gas chromatography. RESULTS: The mean BDNF content of 2.9 ± 0.7 ng/mL in PC was noted to increase to 56.2 ± 2.4 ng/mL after S/D treatment and remained stable during oil extraction. Approximately 70% of the BDNF content was recovered after C18 chromatography. BDNF did not bind to DEAE‐Sepharose and was almost completely adsorbed by charcoal. Chromatography on SP‐Sepharose yielded a highly enriched 13‐kDa mature BDNF fraction that was more than 170‐fold purified, with a mean of 137 ± 29.4 ng/mL and 82% chromatographic recovery, devoid of detectable TnBP and Triton X‐45. Pro‐BDNF and TrkB proteins were not detected in the PLT extracts. CONCLUSION: We obtained a S/D‐treated, highly enriched mature PLT‐derived BDNF fraction that could help unveil the pharmacokinetics, pharmacodynamic, and potential therapeutic applications of the BDNF neurotrophin.     

Subclinical left ventricular systolic dysfunction detected in obstructive sleep apnea with automated function imaging and its association with nocturnal hypoxia

Sleep and Breathing - Early detection of left ventricular (LV) dysfunction is crucial in obstructive sleep apnea (OSA) due to its close relationship with cardiovascular diseases. Global...     

牙膏为可疑变应原的慢性唇炎76例患者标准抗原及牙膏斑贴试验结果分析及方法探索

目的探索牙膏为可疑变应原的慢性唇炎患者病因中变应原及牙膏斑贴试验方法。方法通过病史询问与斑贴试验,对76例牙膏为可疑变应原的慢性唇炎患者进行标准抗原及可疑牙膏原物斑贴试验,对可疑牙膏原物采用4种封包时间,分别为1,2,4及48h,并于48,72,120h进行观察,记录不同时间斑贴试验结果。结果 76例牙膏为可疑变应原的慢性唇炎患者中,46例标准抗原斑贴试验阳性,阳性率60.53%;牙膏原物封包48h在72h观察,36例可疑牙膏原物斑贴试验阳性,阳性率47.37%;牙膏原物封包2,4和48h在72h,120h观察结果差异无统计学意义。结论牙膏为可疑变应原的慢性唇炎患者宜常规进行筛查系列标准抗原和近期使用的牙膏进行斑贴试验;采用牙膏原物封包2~4h,并于48~72h后进行观察,基本可排除原发刺激反应,阳性结果有较高的临床相关性。     

Phase II study of combination doxorubicin, interferon-alpha, and high-dose tamoxifen treatment for advanced hepatocellular carcinoma

BACKGROUND/AIMS: Our previous studies showed that high-dose tamoxifen may improve the therapeutic efficacy of doxorubicin (HTD regimen) in hepatocellular carcinoma. Interferon-alpha, either as a single-agent treatment or as a biochemical modulator, has also been reported to be effective in the treatment of hepatocellular carcinoma. In this study, we sought to clarify if the addition of Interferon-alpha2b to HTD regimen could further improve the control of advanced hepatocellular carcinoma. METHODOLOGY: Eligible patients had unresectable and non-embolizable hepatocellular carcinoma, objectively measurable tumors, adequate hemogram and major organ function, age > or = 75 year, and a Karnofsky performance status > or = 60%. The treatment included oral tamoxifen 40 mg/m2, q.i.d., Day 1-7; interferon-alpha2b subcutaneous injection, 5 MU/m2, q.d. (Day 3-5) and 3 MU/m2, q.o.d. (Day 6-21); and intravenous doxorubicin 60 mg/m2, Day 4, repeated every 4 weeks. RESULTS: From May 1997 through July 2002, a total of 30 patients were enrolled, 25 of whom were eligible for assessment of response and toxicity. These included 20 men and 5 women, with a median age of 45 years. They received an average of 3.5 (range: 1-8) courses of chemotherapy. Grade 3-4 leukopenia and Grade 3-4 thrombocytopenia developed in 46.7% and 51.0% of treatment courses, respectively. Gastrointestinal toxicity was generally mild. One patient achieved a complete remission and remained disease-free at this report, with a progression-free survival of 49 months at last follow-up in September 2002. Five patients achieved a partial remission, with a median progression-free survival of 7 months. The total response rate was 24% (95% confidence interval 9.4-45.1%). Median survival for all 25 patients was 6.0 months and the 1-year survival rate was 16%. CONCLUSIONS: Combination of interferon-alpha2b, high-dose tamoxifen, and doxorubicin is an effective treatment for advanced hepatocellular carcinoma. However, the data does not support that addition of interferon-alpha2b is superior to HTD regimen alone.