Opsoclonus-myoclonus syndrome following long-term use of cyclosporine

Background: Cyclosporine A (CsA) is a widely used immunosuppressive agent that may provoke unexpected neurologic complications. The mechanism is unclear and variable intervals have been reported between CsA administration and onset of the related side effects. Here, we describe a case of delayed-onset CsA neurotoxicity presenting as opsoclonus-myoclonus syndrome (OMS).

Case details: A 37-year-old woman with a two-week period of opsoclonus and upper extremity myoclonus was admitted to our hospital. The patient had been taking CsA for 17 years after receiving a kidney transplant. Further evaluation did not reveal any other abnormalities. Seven days after switching from CsA to tacrolimus, in the absence of additional immune-modulating therapy, her neurologic symptoms improved considerably.

Conclusion: This is the case of delayed, long-term complications of CsA presenting as OMS. Symptoms resolved by substituting CsA with another immunomodulating drug. The etiology of the neurologic complications may involve paradoxically-enhanced delayed-type hypersensitivity.     

Ticlopidine-associated aplastic anemia

 Serious hematologic complications associated with ticlopidine have been reported, including aplastic anemia. We report here an additional case of fatal aplastic anemia due to ticlopidine. A 66-year-old male patient developed fever and pancytopenia 2 months after ticlopidine was started. Despite the administration of granulocyte colony-stimulating factor (G-CSF) and broad-spectrum antibiotics, as well as aggressive red cell and platelet transfusions, the patient died 16 days after admission due to septic shock. Eighteen other cases of ticlopidine-induced aplastic anemia published in the English literature are also reviewed and presented here. Eight of the total 19 patients (including the one reported here) have died, mostly due to infection. Of the seven who received supportive treatment only, four had spontaneous recovery. Nine cases were treated with G-CSF or granulocyte-macrophage colony-stimulating factor (GM-CSF), and response was observed in only four of them. Several other cases were treated with high-dose corticosteroids or androgens; however, it was not possible to evaluate the efficacy of these treatments because of the limited number of cases. In the absence of satisfactory treatment for ticlopidine-induced aplastic anemia at present, it may be reasonable to try antilymphocyte globulin or cyclosporine. Also, great efforts should be made in the prevention and management of infection accompanying this disease. Received: 2 November 1997 / Accepted: 12 January 1998     

Novel adjunctive treatments of myocardial infarction

Myocardial infarction is a major cause of death and disability worldwide and myocardial infarct size is a major determinant of prognosis. Early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome,but reperfusion may induce further myocardial damage itself. Development of adjunctive therapies to limit myocardial reperfusion injury beyond opening of the coronary artery gains increasing attention. A vast number of experimental studies have shown cardioprotective effects of ischemic and pharmacological conditioning,but despite decades of research,the translation into clinical effects has been challenging. Recently published clinical studies,however,prompt optimism as novel techniques allow for improved clinical applicability. Cyclosporine A,the GLP-1 analogue exenatide and rapid cooling by endovascular infusion of cold saline all reduce infarct size and may confer clinical benefit for patients admitted with acute myocardial infarcts. Equally promising,three follow-up studies of the effect of remote ischemic conditioning(RIC) show clinical prognostic benefit in patients undergoing coronary surgery and percutaneous coronary intervention. The discovery that RIC canbe performed noninvasively using a blood pressure cuff on the upper arm to induce brief episodes of limb ischemia and reperfusion has facilitated the translation of RIC into the clinical arena. This review focus on novel advances in adjunctive therapies in relation to acute and elective coronary procedures.     

The effects of systemic cyclosporine in acute Stevens-Johnson syndrome/toxic epidermal necrolysis on ocular disease

PurposeTo evaluate the effect of systemic cyclosporine (CsA) on ocular disease in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients.MethodsIn this retrospective, comparative cohort study at a single center, patients with a diagnosis of SJS/TEN and with at least 3 months of follow up were divided into two groups: those who received systemic CsA and those who did not receive systemic CsA. Best-corrected visual acuity (BCVA) and chronic ocular surface complications score (COCS) at final follow-up were compared between the two groups.ResultsThe median age and follow-up period of patients was 29 years (range, 1.5–71 years) and 16.8 months (range, 3.67–91.58 months), respectively. BCVA, COCS, meibomian gland dysfunction, limbal stem cell deficiency, and the need for mucous membrane grafting and scleral lenses were not significantly different between patients who received systemic CsA as compared to patients who did not receive systemic CsA.ConclusionsIn this small cohort of patients with SJS/TEN, we could identify no association between the use of systemic CsA as a component of their initial therapy and chronic ocular complications.     

Calcium Channel Blockade in Rats with Cyclosporine-Induced Vasoconstriction

Calcium channel blockade has been found to attenuate nephrotoxicity of cyclosporine. However, it is not known whether intrarenal vasoconstriction caused by cyclosporine is totally mediated by vascular smooth muscle calcium influx. To study the protective effects of two calcium blockers on cyclosporine-induced intrarenal vasoconstriction and renal microvascular blood flow, hydronephrotic rat kidneys were suspended in an environmentally controlled tissue bath. Renal microvessel diameters and microvascular blood flow were determined by in vivo videomicroscopy and Doppler velocimetry. Calcium channel blockade was achieved by adding verapamil hydrochloride (5.6 ± 10-⁵ M) or diltiazem hydrochloride (2.8 × 10-⁵ M) to the tissue bath, which respectively resulted in a 15 ± 2% and 16 ± 3% interlobular arteriolar dilation, a 13 ± 3% and 12 ± 2% afferent arteriolar dilation, and a 60 ± 8% and 46 ± 14% increase in interlobular blood flow. When cyclosporine (1.7 × 10-³ M) was added to the tissue bath, there was a constriction of the interlobular arterioles to 4 ± 3% below baseline in rats receiving verapamil and 9 ± 3% below baseline in rats receiving diltiazem. Microvascular blood flow was reduced by the addition of cyclosporine to 3 ± 4% above original baseline values in the verapamil group and 22 ± 6% below baseline in the diltiazem group. Afferent arterioles were similarly constricted by cyclosporine. The results indicate that calcium blockade causes preglomerular vasodilation and protects the microvascular blood flow induced by cyclosporine. Since verapamil or diltiazem did not prevent arteriolar constriction as observed when cyclosporine was added, it was concluded that the mechanism of acute cyclosporine-induced vasoconstriction is not solely mediated by vascular smooth muscle calcium influx through potential dependent channels.     

环孢素A治疗再生障碍性贫血的临床疗效观察

目的针对再生障碍性贫血患者采用环孢素A治疗的临床疗效进行实验观察。方法把在2018年3月至2019年9月期间在我院开始治疗的再生障碍性贫血患者作为了观察的对象,共50例,按照患者治疗药物的不同将患者分配成不同的小组,包括干预组(环孢素A治疗)以及常规组(常规药物治疗),对比两组患者治疗后的贫血改善现象、并发症出现率以及临床疗效。结果干预组患者在治疗后,患者的临床疗效、贫血指标明显更高,干预组患者出现肝功能损害等并发症的几率明显低于常规组患者,两组患者之间相关指标对比后存在明显的差异,对比差异有统计学意义(P<0.05)。结论对再生障碍性贫血患者采用环孢素A药物进行治疗,可提高患者临床治疗总有效果,同时减少患者治疗期间的并发症出现,帮助改善患者贫血现象,有利于患者恢复健康。     

环孢素A联合司坦唑醇片加中药补肾益气为主治疗慢性再生障碍性贫血的临床效果研究

目的环孢素A联合司坦唑醇片加中药补肾益气为主治疗慢性再生障碍性贫血的临床疗效。方法选取2011年3月至2013年3月于我院接受治疗的慢性再生障碍性贫血患者60例,将其随机分为对照组和观察组,每组各30例,对照组单用环孢素A联合司坦唑醇片进行治疗,观察组患者在此基础上加用中药补肾益气(炙黄芪45 g,熟地20 g,山药15 g,山萸肉10 g,丹皮9 g,茯苓10 g,泽泻10 g,当归9 g,党参20 g,白术10 g,女贞子20 g,旱莲草20 g,炙甘草6 g)进行治疗,两组均治疗6个月,并以临床疗效(治疗总有效率)、血象参数、治疗起效时间及不良反应率为考察指标对两组患者的治疗效果进行比较分析。结果经过治疗,观察组在治疗总有效率、血象参数、治疗起效时间方面明显优于对照组,二者差异显著,具有统计学意义,P<0.05;在不良反应发生率方面两组类似,差异不显著,P>0.05。结论环孢素A联合司坦唑醇片加中药补肾益气治疗慢性再生障碍性贫血起效快、疗效显著,提高机体免疫力,临床用药相关不良反应小,比单纯环孢素A联合司坦唑醇片总有效率明显上升,值得临床推广应用。     

The effects of prednisone and steroid-sparing agents on decay accelerating factor (CD55) expression: Implications in myasthenia gravis

Decay accelerating factor (DAF) expression at the muscle endplate is an important defence against complement-mediated damage in myasthenia gravis. Previously we implicated the c.-198C > G DAF polymorphism with the development of treatment-resistant myasthenia-associated ophthalmoplegia by showing that the C > G DAF polymorphism prevented lipopolysaccharide-induced upregulation of lymphoblast DAF. We postulated that drugs used in myasthenia gravis may increase the susceptibility of extraocular muscles to complement-mediated damage and studied their effects on endogenous DAF using patient-derived lymphoblasts as well as mouse myotubes. We show that prednisone repressed C > G DAF expression in lymphoblasts and increased their susceptibility to cytotoxicity. Methotrexate, but not azathioprine or cyclosporine, increased DAF in C > G lymphoblasts. In mouse myotubes expressing wild-type Daf, prednisone also repressed Daf expression. Although cyclosporine, azathioprine, and methotrexate increased muscle Daf levels when used alone, upon co-treatment with prednisone only azathioprine maintained myotube Daf levels close to basal. Therefore, prednisone negatively influences DAF expression in C > G lymphoblasts and in myotubes expressing wild-type Daf. We speculate that myasthenic individuals at risk of developing the ophthalmoplegic complication, such as those with C > G DAF, may have inadequate endogenous levels of complement regulatory protein protection in their extraocular muscle in response to prednisone, increasing their susceptibility to complement-mediated damage.     

Cancer risk of immunosuppressants in manufacturing

During the chemical and pharmaceutical production of active pharmaceutical substances which are intended for immunosuppressive therapy, the employees may be exposed to these substances via inhalation. Immunosuppressants are linked to development of certain types of cancers e.g., lymphoma or skin cancer in transplant patients. The development of these cancers in patients is linked to the level of immunosuppression needed for transplantation in order to avoid organ rejection. Below these levels, with the immune system functioning uninhibited, cancer is unlikely to develop.