Rekonvaleszentenserumbehandlung der Encephalitis und Frage Ihrer ätiologie

Zusammenfassung Auch die sporadischen Fälle von Economo-Encephalitis sollen — zur Unterscheidung von anderen sporadischen Encephalitiden — als Encephaliticaepidemica bezeichnet werden, weil dieser Begriff als Krankheitsbezeichnung allgemein eingeführt ist.Zwei frische Fälle (1930) typischer schwerer kindlicher Economo-Encephalitis wurden durch i.m. Injektion von R.S. der Göttinger Encephalitisstation prompt beeinflußt und vorläufig geheilt.Jeder frische Fall von epidemischer Encephalitis soll auch im Kindesalter alsbald mit R.S. behandelt werden.Die Ergebnisse der Hornhautimpfungen vonKnauer undJaensch bilden keinen hinreichenden Grund, etwa aus ätiologischen Gründen die nosologische Krankheitseinheit Encephalitica epidemica in ihrer bisherigen Form aufzugeben.Klinischer Verlauf und Obduktionsbefund zweier Fälle, die das Bild der abakteriellen eitrigen Meningitis darboten, werden mitgeteilt. Keine Beeinflussung durch das Göttinger R.S., Hornhautimpfung mit den Liquores (Prof.Grüter) negativ.Nach einem Vortrage, gehalten auf der Tagung Südwestdeutscher und Rheinischwestfälischer Kinderärzte in Gießen am 12. April 1931.     

Vaccine-induced systemic and mucosal T cell immunity to SARS-CoV-2 viral variants

The first-generation COVID-19 vaccines have been effective in mitigating severe illness and hospitalization, but recurring waves of infections are associated with the emergence of SARS-CoV-2 variants that display progressive abilities to evade antibodies, leading to diminished vaccine effectiveness. The lack of clarity on the extent to which vaccine-elicited mucosal or systemic memory T cells protect against such antibody-evasive SARS-CoV-2 variants remains a critical knowledge gap in our quest for broadly protective vaccines. Using adjuvanted spike protein–based vaccines that elicit potent T cell responses, we assessed whether systemic or lung-resident CD4 and CD8 T cells protected against SARS-CoV-2 variants in the presence or absence of virus-neutralizing antibodies. We found that 1) mucosal or parenteral immunization led to effective viral control and protected against lung pathology with or without neutralizing antibodies, 2) protection afforded by mucosal memory CD8 T cells was largely redundant in the presence of antibodies that effectively neutralized the challenge virus, and 3) “unhelped” mucosal memory CD8 T cells provided no protection against the homologous SARS-CoV-2 without CD4 T cells and neutralizing antibodies. Significantly, however, in the absence of detectable virus-neutralizing antibodies, systemic or lung-resident memory CD4 and “helped” CD8 T cells provided effective protection against the relatively antibody-resistant B1.351 (β) variant, without lung immunopathology. Thus, induction of systemic and mucosal memory T cells directed against conserved epitopes might be an effective strategy to protect against SARS-CoV-2 variants that evade neutralizing antibodies. Mechanistic insights from this work have significant implications in the development of T cell–targeted immunomodulation or broadly protective SARS-CoV-2 vaccines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to exert devastating impacts on the human life, with >280 million infections and over 5.4 million deaths to date. Although there are millions of convalescent people with some measure of immunity and 8.8 billion doses of vaccine administered to date, further threats of widespread severe COVID-19 disease looms heavily as immunity induced by infection or the first-generation vaccines may not provide effective and durable protection, either due to waning immunity or due to poor antibody cross-reactivity to new variants (1–5).It is clear that virus-neutralizing antibodies provide the most effective protection to SARS-CoV-2, following vaccination or recovery from infection (6). However, T cell–based protection against SARS-CoV-2 has become a central focus because T cells recognize short amino acid sequences that can be conserved across viral variants (7–9). Indeed, T cells in convalescent COVID-19 patients have shown robust responses that are directed at multiple viral proteins, and depletion of these T cells delayed SARS-CoV-2 control in mice (10–12). These data suggest a protective role for T cells in COVID-19 infection. In effect, what constitutes an effective, an ineffective, or a perilous T cell response to SARS-CoV-2 in lungs remains poorly defined. Controlled studies in laboratory animals are of critical importance to elucidate the role and nature of T cells in lungs during SARS-CoV-2 virus infection and in protective immunity.Based on the differentiation state, anatomical localization and traffic patterns, memory T cells are classified into effector memory (T_EM), central memory (T_CM), and tissue-resident memory (T_RM) (13, 14). There is accumulating evidence that airway/lung-resident T_RMs, and not migratory memory T cells (T_EMs) are critical for protective immunity to respiratory mucosal infections with viruses, such as influenza A virus (IAV) and respiratory syncytial virus (15–21). Development of T_RMs from effector T cells in the respiratory tract requires local antigen recognition and exposure to critical factors, such as transforming growth factor (TGF)-β and interleukin (IL)-15 (15). Therefore, mucosal vaccines are more likely to elicit T_RMs in lungs than parenteral vaccines (22, 23). A subset of effector T cells in airways of COVID-19 patients display T_RM-like features (24), but the development of T_RMs or their importance in protective immunity to reinfection are yet to be determined. Furthermore, all SARS-CoV-2 vaccines in use are administered parenterally and less likely to induce lung T_RMs. While depletion of CD8 T cells compromised protection against COVID-19 in vaccinated rhesus macaques (25), the relative effectiveness of vaccine-induced systemic/migratory CD8 T cell memory vs. lung/airway T_RMs in protective immunity to COVID-19 is yet to be defined.In this study, using the K18-hACE2 transgenic (tg) mouse model of SARS-CoV-2 infection, we have interrogated two key aspects of T cell immunity: 1) the requirements for lung-resident vs. migratory T cell memory in vaccine-induced immunity to SARS-CoV-2; and 2) the role of lung-resident memory CD4 vs. CD8 T cells in protection against viral variants in the presence or absence of virus-neutralizing antibodies. Studies of mucosal versus systemic T cell–based vaccine immunity using a subunit protein-based adjuvant system that elicits neutralizing antibodies and T cell immunity, demonstrated that: 1) both mucosal and parenteral vaccinations provide effective immunity to SARS-CoV-2 variants; 2) CD4 T cell–dependent immune mechanisms exert primacy in protection against homologous SARS-CoV-2 strain; and 3) the development of spike (S) protein-specific “unhelped” memory CD8 T cells in the respiratory mucosa are insufficient to protect against a lethal challenge with the homologous Washington (WA) strain of SARS-CoV-2. Unexpectedly, we found that systemic or mucosal lung-resident memory CD4 and “helped” CD8 T cells engendered effective immunity to the South African B1.351 β-variant in the apparent absence of detectable mucosal or circulating virus-neutralizing antibodies. Taken together, mechanistic insights from this study have advanced our understanding of viral pathogenesis and might drive rational development of next-generation broadly protective SARS-CoV-2 vaccines that induce humoral and T cell memory.     

高效液相色谱法测定四川粉葛中葛根素的含量

目的：采用HPLC法测定四川粉葛中葛根素的含量。方法：色谱柱为依利特C18柱（4．6min&;#215;150mm,5μm）,流动相为甲醇-水（25：75）,流速为0．8ml／min,检测波长为250nm,柱温为25℃。结果：葛根素在0．0880～0．7040μg范围内峰面积与进样量呈良好的线性关系,回归方程为A=336．35X-1．7716,r=1．0000,其平均同收率为100．01％,RSD为0．14％（n=6）。结论：该方法简便易行,结果准确,可用于四川粉葛药材的质量控制。     

术前血糖水平对糖尿病患者行输尿管软镜碎石术后发生感染相关并发症的影响

观察2型糖尿病（T2DM）患者行输尿管软镜碎石术（FURL）后出现感染相关并发症的影响因素,探讨T2DM患者术前血糖水平与发生术后感染相关并发症的关系,为T2DM患者在接受FULR术后发生感染相关并发症的早期预防及治疗提供参考。     

寰椎椎弓根螺钉置钉技巧探讨

[目的]探讨寰椎椎弓根螺钉固定治疗寰枢椎不稳的置钉技巧。[方法]总结2000年10月～2008年9月应用寰椎椎弓根螺钉技术治疗寰枢椎不稳患者66例,置钉132枚。术中在直视下依据手感行寰椎椎弓根螺钉置钉,复位固定。[结果]本组66例132枚螺钉均成功置入,复位固定满意。术中未发现脊髓、神经根、椎动脉等损伤。术后患者症状及神经脊髓功能均有不同程度恢复。96枚螺钉术后行CT检查,其中91枚位置良好(94.89%)。全部病例内固定无松动、断裂,植骨均融合。[结论]术前影像学测量,术中显露寰椎后弓、直视下依据手感置钉、X线确定进钉方向,是安全置钉的技巧。     

上调肝脏HO-1抑制肥大细胞脱颗粒减轻大鼠肝脏缺血再灌注损伤

目的 探索HO-1对肝脏缺血再灌注损伤中肥大细胞脱颗粒的影响。方法 将20只SD大鼠随机分成4组：假手术组（Sham组）,缺血再灌注损伤组（I/RI组）,HO-1诱导剂钴原卟啉组(CoPP组,术前24h给予CoPP,5 mg/kg)及HO-1抑制剂锌原卟啉组(ZnPP组,术前24h给予ZnPP,20 mg/kg)。建立大鼠缺血再灌注损伤模型,各组于再灌注后2h收集标本。RT-PCR检测肝脏组织HO-1 mRNA表达,Western blot检测肝脏组织HO-1蛋白表达;测定血清中ALT、AST水平;肝脏组织甲苯胺蓝染色检测肥大细胞脱颗粒数量,HE染色评价肝脏组织损伤情况。结果 与Sham组相比,I/RI组、CoPP组、ZnPP组大鼠组织HO-1 RNA和蛋白表达增加,血清ALT、AST水平升高,肥大细胞脱颗粒数量增多,肝脏细胞损伤加重。CoPP组与I/RI组相比,HO-1 mRNA和蛋白表达增加,血清ALT、AST水平减低,肥大细胞脱颗粒数量减少,肝细胞损伤减轻。ZnPP组与I/RI组相比,HO-1 mRNA和蛋白表达减少,血清ALT、AST水平升高,肥大细胞脱颗粒数量增多、肝细胞损伤严重。组间比较差异具有统计学意义(P＜0.05)。结论 HO-1过表达能减轻肝脏I/RI,其机制可能与抑制肝脏组织中肥大细胞脱颗粒有关。     

Neurosurgical procedures in Jehovah's Witnesses: an increased risk?

OBJECTIVE: Because of the growing numbers of members worldwide in the sect of Jehovah's Witnesses, the refusal of blood and blood products due to religious reasons is increasingly encountered in clinical practice. As an alternative to blood transfusion, Jehovah's Witnesses accept blood-free volume substitution, and they sometimes accept the intraoperative reinfusion of autologous blood via a so-called cell saver. The aim of this study was to examine whether the refusal of blood transfusion affects the surgical indications for neurosurgery and whether morbidity and mortality rates are higher after neurosurgical interventions in Jehovah's Witnesses. METHODS: The pre-, intra-, and postoperative hemoglobin and hematocrit values as well as coagulation parameters of a group of Jehovah's Witnesses (n = 103) were compared with those of a valid control group. RESULTS: The total intraoperative blood loss during spinal and intracranial surgery in Jehovah's Witnesses was often less than in controls, which suggests a less traumatic surgical procedure. Hemodynamically relevant blood loss occurred in two spinal and four intracranial interventions. The patients were managed without receiving blood transfusions or blood products, although increased time in the intensive care unit and increased convalescence days were necessary. Mean surgical times were 17.5 minutes longer for spinal interventions and 36.7 minutes longer for intracranial interventions than for patients in the control group. This may be attributed to a more careful and thus slower surgical technique and to longer and more extensive hemostasis. The length of hospitalization was 15% longer for Jehovah's Witnesses than for controls. CONCLUSION: The morbidity and mortality rates for Jehovah's Witnesses undergoing neurosurgery were not higher than those of the control group. Thus, it can be concluded that Jehovah's Witnesses did not have a higher risk when microsurgical techniques and extensive anesthetic monitoring were applied during neurosurgery. Because the surgical success rate for Jehovah's Witnesses corresponded to that of the control group, the increase in costs because of longer treatment times is compensated in the long run by avoiding a lengthier illness, sometimes with more expensive conservative therapy.     

Testicular tumours in children: a single-institutional experience

OBJECTIVE: To report our experience of testicular and paratesticular tumours in children, as such tumours are rare, and historically yolk sac tumour has been described as the most common lesion in children, but recent reports suggest that benign testicular lesions might be more common. PATIENTS AND METHODS: We reviewed retrospectively the records of children treated for testicular tumours from 1998 to 2005. The patients' age, clinical presentation, diagnostic procedures, treatment methods, histopathological findings, and outcome were recorded. Patients aged>144 months and those with non-primary metastatic lesions were excluded. RESULTS: In all, 11 patients met our criteria, with a mean age of 37 months (range 9 days to 144 months). Pathological analysis revealed teratoma in four patients, yolk sac tumour in two, epidermoid cysts in two, extrarenal nephroblastomatosis in one, and paratesticular rhabdomyosarcomas in two. The most common clinical presentation was a painless testicular mass. Depending on the clinical presentation and pathology, scrotal ultrasonography, tumour markers (alpha-fetoprotein and beta-human chorionic gonadotrophin), and/or staging computed tomography (CT) were obtained in eight patients. All patients had a radical orchidectomy. Three patients had elevated tumour markers that normalized after orchidectomy. CT revealed extensive mediastinal adenopathy in one patient with rhabdomyosarcoma. Chemotherapy was administered to both patients with rhabdomyosarcoma. CONCLUSION: Although there were few patients, most of the lesions were benign tumours, with the most common histological subtype being teratoma. As both malignant and paratesticular lesions occurred at a significant frequency, we would continue to advocate an initial radical inguinal approach at which time testis-sparing could be considered if the preoperative evaluation was favourable, and frozen-section analysis at the time of surgery confirms a benign lesion.