β-榄香烯术前区域动脉灌注对乳腺癌组织的抑制作用及其对细胞凋亡和增殖的影响

目的 :观察中药莪术有效提取物 β -榄香烯术前区域动脉灌注对乳腺癌组织的抑制作用及其对细胞凋亡和增殖的影响。方法 :临床观察给药后肿块的改变并应用末端转移酶介导的脱氧核苷酸末端标记法(TUNEL法 )和增殖细胞核抗原 (PCNA)免疫组化检测方法 ,观察术前 β -榄香烯治疗组 14例和一期手术组 17例乳腺癌标本的凋亡指数、增殖指数和分裂指数的差异。结果 :β -榄香烯治疗组凋亡指数 (7.97±1.50 )明显高于一期手术对照组 (2 .2 6± 0 .4 9) ,两组比较差异有显著性 (P <0 .0 1) ;β -榄香烯治疗组增殖细胞核抗原指数 (4 4 .54± 9.99)与对照组 (4 2 .80± 6 .78)比差异无显著性 (P >0 .0 5) ;治疗组的分裂指数(3.92± 1.4 4 )与对照组 (3.88± 1.0 8)比 ,差异无显著性 (P >0 .0 5)。 14例术前 β -榄香烯治疗组等级相关分析凋亡指数与肿块缩小程度呈正相关 (r=- 0 .72 9)。结论 :给乳腺癌患者术前区域动脉灌注 β -榄香烯可缩小乳腺癌局部肿块其机理可能与诱导乳腺癌细胞凋亡有关     

选择性动脉置泵区域灌注化疗治疗不能切除的胃底贲门癌

目的 探讨术中选择性动脉内置泵区域灌注化疗治疗不能切除的胃底贲门癌的疗效。方法 对手术证实不能切除的，经选择性动脉内置泵灌注化疗治疗的38例晚期胃底贲门癌的临床资料进行回顾性研究。结果 吞咽困难缓解率达100％，腹痛缓解率达88．5％（23／26），肿瘤缩小率84．2％（32／38），其中5例经再次手术行根治性切除。1年生存率71．1％，2年生存率21．1％，其中3例生存3年。结论 超选择性动脉内置泵区域灌注化疗是治疗晚期胃底贲门癌的有效方法，可以延长患者的带瘤生存期，甚至可以再次手术切除。     

Osteomalacia as a Complication of Intravenous Iron Infusion: A Systematic Review of Case Reports

Randomized control trials (RCTs) have shown that certain intravenous iron preparations can induce high levels of fibroblast growth factor 23 (FGF-23) and persistent hypophosphatemia. Repeated iron infusions may lead to prolonged hypophosphatemia and osteomalacia events not captured by RCTs. Several previous case reports have described skeletal adverse effects after repeated iron infusions. To characterize these effects, we conducted a systematic review of case reports. MEDLINE, Embase, Web of Science, and Cochrane databases were searched in March 2021. We selected case reports of patients ≥16 years old. Study quality was assessed using the tool from Murad and colleagues. We report the results in a narrative summary. We identified 28 case reports, reporting 30 cases. Ages ranged from 28 to 80 years (median 50 years). Most patients (n = 18) received ferric carboxymaltose (FCM), whereas 8 received saccharated ferric oxide (SFO) and 3 received iron polymaltose (IPM). All but 2 cases had more than five infusions (range 2 to 198, median 17). The lowest phosphate levels ranged from 0.16 to 0.77 mmol/L (median 0.36 mmol/L). Intact FGF-23 (iFGF-23) was high when measured. Serum 25OH vitamin D was low in 10 of 21 cases measured and 1,25(OH)₂ vitamin D in 12 of 18. Alkaline phosphatase was high in 18 of 22 cases. Bone or muscle pain was reported in 28 of the 30 cases. Twenty patients had pseudofractures, 9 had fractures, and 6 patients had both. All 15 available bone scans showed focal isotope uptake. Case reports tend to report severe cases, so potential reporting bias should be considered. Osteomalacia is a potential complication of repeated iron infusion, especially in patients with gastrointestinal disorders receiving prolonged therapy. Pain and fractures or pseudofractures are common clinical findings, associated with low phosphate, high iFGF-23, high alkaline phosphatase, and abnormal isotope bone scan. Discontinuing or switching the iron formulation was an effective intervention in most cases. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

Clinical data suggest concomitant therapy with bisphosphonates and parathyroid hormone (PTH) may blunt the anabolic effect of PTH; rodent models suggest that infrequently administered bisphosphonates may interact differently. To evaluate the effects of combination therapy with an intravenous infusion of zoledronic acid 5 mg and daily subcutaneous recombinant human (rh)PTH(1–34) (teriparatide) 20 µg versus either agent alone on bone mineral density (BMD) and bone turnover markers, we conducted a 1‐year multicenter, multinational, randomized, partial double‐blinded, controlled trial. 412 postmenopausal women with osteoporosis (mean age 65 ± 9 years) were randomized to a single infusion of zoledronic acid 5 mg plus daily subcutaneous teriparatide 20 µg (n = 137), zoledronic acid alone (n = 137), or teriparatide alone (n = 138). The primary endpoint was percentage increase in lumbar spine BMD (assessed by dual‐energy X‐ray absorptiometry [DXA]) at 52 weeks versus baseline. Secondary endpoints included change in BMD at the spine at earlier time points and at the total hip, trochanter, and femoral neck at all time points. At week 52, lumbar spine BMD had increased 7.5%, 7.0%, and 4.4% in the combination, teriparatide, and zoledronic acid groups, respectively (p < .001 for combination and teriparatide versus zoledronic acid). In the combination group, spine BMD increased more rapidly than with either agent alone (p < .001 versus both teriparatide and zoledronic acid at 13 and 26 weeks). Combination therapy increased total‐hip BMD more than teriparatide alone at all times (all p < .01) and more than zoledronic acid at 13 weeks (p < .05), with final 52‐week increments of 2.3%, 1.1%, and 2.2% in the combination, teriparatide, and zoledronic acid groups, respectively. With combination therapy, bone formation (assessed by serum N‐terminal propeptide of type I collagen [PINP]) increased from 0 to 4 weeks, declined minimally from 4 to 8 weeks, and then rose throughout the trial, with levels above baseline from 6 to 12 months. Bone resorption (assessed by serum β‐C‐telopeptide of type I collagen [β‐CTX]) was markedly reduced with combination therapy from 0 to 8 weeks (a reduction of similar magnitude to that seen with zoledronic acid alone), followed by a gradual increase after week 8, with levels remaining above baseline for the latter half of the year. Levels for both markers were significantly lower with combination therapy versus teriparatide alone (p < .002). Limitations of the study included its short duration, lack of endpoints beyond DXA‐based BMD (e.g., quantitative computed tomography and finite‐element modeling for bone strength), lack of teriparatide placebo, and insufficient power for fracture outcomes. We conclude that while teriparatide increases spine BMD more than zoledronic acid and zoledronic acid increases hip BMD more than teriparatide, combination therapy provides the largest, most rapid increments when both spine and hip sites are considered. © 2011 American Society for Bone and Mineral Research.     

胃癌手术后局部灌注化疗预防局部复发和肝转移的临床研究

目的　探讨胃癌术后局部灌注化疗预防局部复发和肝转移的价值。方法　将收治的 3 5 2例胃癌术前随机分为两组,治疗组术后行局部动脉灌注化疗 ( 1 8 4例 );对照组术后行全身静脉化疗( 1 6 8例 ),对两组的疗效进行比较。结果　随访时间 3 ~ 6 年,随访 3 2 8 例,失访 2 4 例,随访率93. 2%。治疗组 1, 3, 5 年生存率分别为 9 5. 7% , 7 8. 3% , 4 6. 3% ;对照组是 8 6. 8% , 4 8. 2% ,21. 4%。局部复发率和肝转移率治疗组为 9. 2% , 1 2. 5% ,对照组为 2 2. 0% , 2 6. 8%。两组上述各项指标差异均有显著意义 (均P< 0. 0 1 )。结论　局部灌注化疗是胃癌术后预防局部复发和肝转移的一种有效方法,其疗效明显优于术后全身静脉化疗,且毒副作用小。     

Long-term neuroprotection induced by regional brain cooling with saline infusion into ischemic territory in rats: a behavioral analysis

Abstract

The neuroprotective effect of hypothermia has long been recognized. Our recent studies have demonstrated the significant therapeutic value of local brain cooling in the ischemic territory prior to reperfusion in stroke, with reduced infarction and inflammatory responses up to 48 hours of reperfusion. The goal of this study was to determine if local brain cooling, produced by infusion of cold saline, could induce long-term functional improvement after stroke. A hollow filament was used to block the middle cerebral artery (MCA) for 3 hours, and then to locally infuse the ischemic territory with 6 ml cold saline (20°C) for 10 minutes prior to reperfusion. This brain cooling infusion induced a significant (p < 0.01) decrease in neurologic deficits and significantly (p < 0.01) improved motor behavior in ischemic rats after 14 days of reperfusion, compared with ischemic rats without local cold saline infusion. This improvement continued for up to 28 days after reperfusion. No significant difference in motor performance was observed between the brain cooling infusion and normal control groups. Significant (p < 0.01) reductions in infarct volume were also evident. In conclusion, a local cerebral hypothermia induced by local saline infusion prior to reperfusion produced a long-term functional recovery after ischemic stroke. A therapeutic procedure, which combines prereperfusion infusion into an ischemic region with coincident cerebral hypothermia and perhaps subsequent recanalization of an occluded intracranial vessel, may improve the outcome for stroke patients.     

Bone material properties in actively bone‐forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once‐yearly Zoledronic acid

Zoledronic acid (ZOL), a third‐generation aminobisphosphonate, showed pronounced antifracture efficacy in a phase III clinical trial [Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly—Pivotal Fracture Trial (HORIZON‐PFT)] when administered yearly (5‐mg infusions of ZOL), producing significant reductions in morphometric vertebral, clinical vertebral, hip, and nonvertebral fractures by 70%, 77%, 41%, and 25%, respectively, over a 3‐year period. The purpose of this study was to analyze the biopsies obtained during the HORIZON clinical trial (152 patients, 82 ZOL and 70 placebo) by means of Raman microspectroscopy (a vibrational spectroscopic technique capable of analyzing undecalcified bone tissue with a spatial resolution of approximately 0.6 µm) to determine the effect of ZOL therapy on bone material properties (in particular mineral/matrix ratio, lamellar organization, carbonate and proteoglycan (based on spectral identification of glycosaminoglycan) content, and mineral maturity/crystallinity) at similar tissue age (based on the presence of tetracycline double labels). The results indicated that while ZOL administration increased the mineral/matrix ratio compared with placebo, it also resulted in mineral crystallites with a quality profile (based on carbonate content and maturity/crystallinity characteristics) of younger (with respect to tissue age) bone. Since the comparisons between ZOL‐ and placebo‐treated patients were performed at similar tissue age at actively forming bone surfaces, these results suggest that ZOL may be exerting an effect on bone matrix formation in addition to its well‐established antiresorptive effect, thereby contributing to its antifracture efficacy. © 2011 American Society for Bone and Mineral Research.     

Responses to Different Levels of Esophageal Acidification During Waking and Sleep

The purpose of this study was to assess theeffect of hydrogen ion concentration of intraesophagealinfusions during sleep on acid clearance time andlatency to swallow and arousal responses from sleep. We studied 10 normal volunteers during sleepvia polysomnography and concomitant esophageal pHmonitoring. Sleep prolonged the acid clearance time ofboth pH 3.0 and 1.2. Swallow and arousal latencies were both progressively decreased with decreasing pHof the infusate (P < 0.05, 0.07, respectively). Weconcluded that intraluminal hydrogen ion concentrationcreates an afferent warning stimulus that produces prompt airway-protective responses.     

Slight elevation of baseline intracranial pressure after fluid infusion into CSF space in patients with hydrocephalus

Abstract

Objective: To investigate the elevation of resting cerebrospinal fluid (CSF) pressure recorded after a CSF infusion test in patients with hydrocephalus.

Material and methods: Fifty patients (30 men and 20 women, mean age 68 ± 13 years) with ventriculomegaly and clinical symptoms of normal pressure hydrocephalus have been studied. Lumbar (56%) or intraventricular (44%) computerized infusion studies were performed to investigate the hydrodynamics of CSF. After infusion, the fall in ICP was recorded until a steady-state level was achieved and the difference between pre- and post-infusion resting ICP was calculated (ΔICP).

Results: A positive difference (>2 mm Hg) between post- and pre-infusion resting ICP was identified in 31 infusion tests (62%). The mean value of the difference was 6.7 with an SD of 3.5 mm Hg. The patients who demonstrated this phenomenon had a greater elastance coefficient (p>0.05); ΔICP was positively correlated with age (R=0.27; p=0.03), with the size of the brain's ventricles (R=0.63, p=0.03) and inversely with the severity of clinical impairment (Stein-Langfitt score R=–0.61, p=0.02; normal pressure hydrocephalus score: R=0.54; p<0.05). ΔICP was independent of the site of infusion (lumbar or ventricular).

Conclusion: In patients with a 'stiffer' brain, ICP returns to the resting level after the infusion test at a slightly higher level than before the test. The magnitude of this increase is greater when ventricles are more dilated and clinical symptoms are less severe.