Reversal of granulocyte adherence to nylon fibers using local anesthetic agents: possible application to filtration leukapheresis

The effects of the cationic anesthetic agents tetracaine and lidocaine on granulocyte function, morphology, and adherence to nylon fibers were studied in an attempt to improve current methods of granulocyte collection by filtration leukapheresis (FL). When dissolved in acid- citrate-dextrose (ACD) plasma, these drugs significantly increased granulocyte elution from the fibers in a dose-related fashion. Granulocytes exposed to tetracaine and lidocaine remained more than 95% viable, retained normal bactericidal capacity after the drugs were washed from the cells, and had preserved membrane integrity, as evidenced by the normal ultrastructural appearance of tetracaine- exposed cells and an absence of leakage of lysozyme or lactic dehydrogenase. Granulocytes eluted with the anesthetic agents were rounded in shape with a reduction in the number of filopodial cytoplasmic projections and a relative absence of cytoplasmic vacuolization when compared to granulocytes eluted with ACD plasma alone. Dose-related inhibition of phagocytosis and adherence, which was largely reversible after washing the granulocytes, was noted. Greater than 95% of the lidocaine could be removed from the eluate with a single centrifugation and resuspension, indicating that granulocytes prepared by FL with anesthetic-enhanced elution could be potentially transfusable.     

Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

Stroke mortality and morbidity is expected to rise. Despite considerable recent advances within acute ischemic stroke treatment, scope remains for development of widely applicable neuroprotective agents. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally licensed for the management of Type 2 Diabetes Mellitus, have demonstrated pre-clinical neuroprotective efficacy in a range of neurodegenerative conditions. This systematic scoping review reports the pre-clinical basis of GLP-1RAs as neuroprotective agents in acute ischemic stroke and their translation into clinical trials. We included 35 pre-clinical studies, 11 retrospective database studies, 7 cardiovascular outcome trials and 4 prospective clinical studies. Pre-clinical neuroprotection was demonstrated in normoglycemic models when administration was delayed by up to 24 h following stroke induction. Outcomes included reduced infarct volume, apoptosis, oxidative stress and inflammation alongside increased neurogenesis, angiogenesis and cerebral blood flow. Improved neurological function and a trend towards increased survival were also reported. Cardiovascular outcomes trials reported a significant reduction in stroke incidence with semaglutide and dulaglutide. Retrospective database studies show a trend towards neuroprotection. Prospective interventional clinical trials are on-going, but initial indicators of safety and tolerability are favourable. Ultimately, we propose that repurposing GLP-1RAs is potentially advantageous but appropriately designed trials are needed to determine clinical efficacy and cost-effectiveness.     

Treatment of acute lymphoblastic leukemia in adolescents and a-dults: A retrospective study of 41 patients (1970-1973)

During the period from January 1970 until December 1973, therapy was started in 41 previously untreated adolescents and adults with acute lymphoblastic leukemia. Induction therapy was started with vincristine and prednisone in all patients, resulting in complete remission in 19 and death due to infection during the first month in one case. After 3 wk on these two drugs, the addition of daunorubicin was required in the remaining 21 patients. Fifteen of these obtained remission, one died during induction therapy, and five patients were unresponsive to this therapy, as well as to all subsequent induction schemes. The overall remission rate was 83%. Significantly higher initial leukocyte counts were found in the group treated with vincristine, prednisone, and daunorubicin. Meningeal leukemia prophylaxis, by either periodic methotrexate injections given intrathecally or a combination of cranial irradiation and intrathecally administrated methotrexate, was administered in 29 therapy responders. The median duration of complete remission obtained with various maintenance therapy schemes was 13 mo. No differences were seen in the results obtained in patients between 14 and 20 yr of age and older patients. Twenty-two patients relapsed within 2-37 mo. Relapses were confined to the central nervous system in two cases, to the bone marrow in 18, and to the bone marrow and CNS simultaneously in two. A second remission was obtained in 17 cases (77%). The median survival time of the whole group was 27 mo, as compared with 32 mo for therapy responders and 7 mo for the nonresponders. The percentage and duration of remission and the survival time in our group of adolescents and adults were comparable to those currently being achieved in other centers, but not as good as those reported for children treated with the same protocols.     

Persistent reversed end diastolic flow in the fetal middle cerebral artery: an ominous finding

Fetal persistent middle cerebral artery reversed end diastolic flow is a rare and ominous finding. Previous cases have been associated with intracranial hemorrhage, growth restriction, anaemia, and hepatic anomaly. Intrauterine demise or early neonatal death is a common outcome. We report the case of persistent middle cerebral artery reversed end diastolic flow in a well-grown fetus at 32 weeks’ gestation resulting from acute, severe anaemia due to a large feto-maternal hemorrhage. An emergency cesarean section was performed and the neonate required advanced resuscitation and immediate blood transfusion. Postnatal magnetic resonance imaging confirmed a hemorrhagic parietal infarct and bilateral ischaemic changes in the basal ganglia. This provides further evidence that persistent middle cerebral artery reversed end diastolic flow in any fetus is an ominous finding warranting urgent diagnostic evaluation and/or delivery.     

Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen

We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.     

Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America

BACKGROUNDThere has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important.AIMTo evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODSA standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development.RESULTSAzathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent.CONCLUSIONTreatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection.     

金属对金属大头径微创全髋关节置换术治疗青中年股骨头坏死的临床研究

目的探讨金属对金属（金对金）大头径假体微创全髋关节置换术（THA）治疗青中年股骨头坏死Ⅲ、Ⅳ期的临床疗效。方法本组32例（35髋）青中年股骨头缺血性坏死Ⅲ、Ⅳ期患者,年龄24～59岁,平均45岁,术前髋关节Harris评分平均（37．9±7．5）分;以改良后外侧小切口、肌间隙人路、充分保留关节动力性组织结构为特征的金对金大头径微创THA治疗。术中严格采取正确的假体植入技术,术中保留完整的软骨下骨和髋臼横韧带,击入臼杯时一次性安装成功,正确运用万古霉素预防感染。术后口服利伐沙班片抗凝,术后12h开放负压引流及卧床行功能锻炼,术后第2天拔除引流管后扶拐下地部分负重行走,术后2—3周患者即可弃拐完全负重行走。结果本组32例35髋患者均获随访,随访时间为12个月～6年,平均为4年。所有患者切口均一期愈合,无深静脉血栓形成、关节脱位、坐骨神经损伤、髋臼及股骨疲劳骨折、关节疼痛等严重并发症,X线片示髋关节假体位置均良好,无松动、移位、股骨柄下沉、假体周围骨折等表现。末次随访Harris评分由术前平均（37．9±7．5）分,提高至术后平均（92．2±4．6）分,前后比较有统计学意义（t=44．341,P〈0．05）。所有患者末次随访时髋关节功能明显优于术前,均对治疗效果满意,完全恢复正常生活及工作。结论采用金对金大头径微创THA治疗青中年股骨头坏死Ⅲ、Ⅳ期患者,能够明显降低手术风险,缩短卧床时问,迅速恢复髋关节功能,减少手术并发症,取得了满意的近期临床疗效。随着基础和临床研究的不断深入,金对金大头径髋关节假体的长期疗效还需要进一步探讨。     

腹腔镜巨大前列腺囊腺瘤切除一例报告并文献复习

目的提高对巨大前列腺囊腺瘤的认识。方法回顾性分析收治的1例巨大前列腺囊腺瘤并成功进行腹腔镜切除的临床资料,结合文献复习进行讨论。结果本例患者成功行腹腔镜完整切除,手术时间125min,出血量60ml,术中双侧精囊输精管完整保留,术后会阴部坠胀不适消失,复查精液常规精子数目及活动度正常。已随诊12个月,肿瘤无复发。结论巨大前列腺囊腺瘤罕见,最终确诊要依靠病理诊断,其最有效的治疗是手术完整切除,而腹腔镜途径可作为完整切除的微创手段。