Myelopathies secondary to Sjögren's syndrome: treatment with monthly intravenous cyclophosphamide associated with corticosteroids

OBJECTIVE: Central nervous system manifestations in Sj?gren's syndrome (SS) include focal deficits, optic neuritis, and myelopathies. Acute and chronic myelopathies are frequently severe and sometimes respond poorly to corticosteroids. The efficacy of intravenous (IV) cyclophosphamide (CYC) has been suggested in single case reports. METHODS: We describe the potential usefulness of IV CYC in SS patients with severe myelopathies. Fourteen patients [with acute (n = 6) and chronic (n = 8) myelopathies] were treated with monthly CYC infusions (700 mg/m2) in addition to 500 mg of corticosteroids for one year. We evaluated the disability before and after CYC treatment using a walking distance calculation and the Expanded Disability Status Scale (EDSS). RESULTS: CYC treatment was well tolerated in all cases without serious adverse events. Nine patients (including the 6 with acute myelopathy) were improved after CYC treatment. Three patients were stabilized and 2 patients with chronic myelopathies had moderate progression of disability. The mean walking distance increased from 48.2 m before to 180.4 m after CYC treatment (p < 0.02). Mean EDSS score decreased from 6.6 to 5.7 (not significant). We found a correlation between the length of time before CYC treatment and clinical improvement for both the walking distance (p < 0.02) and the EDSS score (p < 0.05). CONCLUSION: Although a randomized multicenter controlled study is warranted to confirm our findings, IV CYC infusions seem to be useful for the treatment of myelopathies secondary to SS, particularly in acute but also in progressive cases. This treatment should be strongly considered as soon as possible when disease progression is observed.     

Myelopathies during the course of multiple myeloma.

BACKGROUND. The development of acute non-lymphoblastic leukaemia (ANLL) or myelodysplastic syndromes (MDS) secondary to treatment of multiple myeloma (MM) is well known. In some cases the simultaneous appearance of MM and ANLL has been described. METHODS. In this series the simultaneous appearance of MM and various myelopathies in 91 untreated patients with MM, and the development of myelopathies during the course of the disease in 72 treated patients were studied. RESULTS. Simultaneous appearance of MM (IgA/lambda) and refractory anaemia with ring sideroblasts (RAS) was observed in one case (1.1%). Development of myelopathies in treated patients with MM was found in 4 out of 72 cases (cumulative risk at 8 years 28.3%). In one case (IgG/lambda MM) a myeloproliferative disorder (MPD) developed 6 years after the initial diagnosis. Cytogenetic analysis was normal. In the second patient (IgG/k MM) a similar MPD was observed 5 years after the initial diagnosis. The karyotype was 46, XX, -5 + t (20;?). The third patient with lambda light chain disease developed RAS 11 months after the initial diagnosis. The karyotype was 46, XY/hypodiploidy + M. Finally, the fourth case (IgG/k MM) developed ANLL (M4) 28 months after the initial diagnosis and the karyotype was 45, XX, -7, t(1;3). CONCLUSIONS. The simultaneous appearance of MM and various myelopathies is unusual and probably represents a neoplastic transformation of a single progenitor in both lymphoid and myeloid malignancies. On the contrary, the development of myelopathies during the course of treated patients is a common phenomenon. The time of development and the cytogenetic findings strongly suggest that they are related to treatment with cytostatics.     

Scapular winging as a symptom of cervical flexion myelopathy

A 23-year-old man complained of weakness of the right arm that he first noted six years prior to his visit. Neurological examination revealed atrophy and weakness of the triceps and serratus anterior muscle on the right side, which resulted in scapular winging on that side. MRI with neck flexion revealed compression of the cervical cord enabling a diagnosis of flexion myelopathy. Proximal muscle weakness and atrophy in flexion myelopathies including Hirayama disease are extremely rare. Here, we report a case of unilateral, proximal upper limb atrophy with scapular winging, attributed to middle cervical flexion myelopathy.     

Intramedullary spinal cord metastases in a patient with small-cell lung cancer

We present the case of a 60-year-old male smoker with gait disturbance, lower limb sensory disturbance, and urinary difficulties of subacute onset and progressive course. He had been diagnosed 10 months earlier with limited stage small-cell lung cancer, had received chemotherapy, thoracic radiotherapy, and prophylactic cranial irradiation, and was in remission on follow-up. Examination revealed bilateral pyramidal tract signs, a T9 sensory level, and loss of vibration and position sense in the lower limbs. Gadolinium-enhanced MRI of the cervical and thoracic spinal cord revealed two enhancing intramedullary lesions consistent with metastases. Intramedullary metastases are exceedingly rare, accounting for only 3.4-6% of myelopathies in cancer patients, and they usually coexist with brain or leptomeningeal metastases. The presence of multiple metastases is even rarer, with two lesions found in only 10% of patients with intramedullary disease.     

A case of ischemic colitis presenting as bloody diarrhea after normal saline enema]

Ischemic colitis is a frequent disorder of large bowel in elderly persons or in debilitated patients with a variable underlying medical problems. Ischemic colitis may result from alterations in the systemic circulation or anatomic or functional changes in the local mesenteric vasculature. In most cases, no specific cause for the ischemic colitis is identified. Cases of ischemic colitis after enema for bowel cleansing have been rarely reported, but there has been no case report after normal saline enema. We report a case of ischemic colitis in a 72-year old patient with well-controlled hypertension, presenting as bloody diarrhea which developed after normal saline enema for preoperative bowel cleansing.     

Milestones in umbilical cord blood transplantation

Since the first human cord blood transplant, performed in 1988, cord blood banks have been established worldwide for collection and cryopreservation of cord blood for allogeneic hematopoietic stem cell transplant. Umbilical cord blood (UCB) has now become one of the most commonly used source of hematopoietic stem cells for allogeneic transplantation. Today a global network of cord blood banks and transplant centers has been established for a common inventory with an estimated 600,000 UCB have been banked and more than 20,000 UCB units distributed worldwide for adults and children with severe hematological diseases. Several studies have shown that the number of cells is the most important factor for engraftment while some degree of HLA mismatches is acceptable. The absence of ethical concern, and the unlimited supply of cells explain the increasing interest of using cord blood for developing regenerative medicine.     

Ischemic colitis masquerading as colonic tumor: case report with review of literature

Ischemic colitis can mimic a carcinoma on computed tomographic (CT) imaging or endoscopic examination. A coexisting colonic carcinoma or another potentially obstructing lesion has also been described in 20% of the cases of ischemic colitis. CT scan can differentiate it from colon cancer in 75% of cases. However, colonoscopy is the preferred method for diagnosing ischemic colitis as it allows for direct visualization with tissue sampling. Varied presentations of ischemic colitis have been described as an ulc...     

Spinal cord ischemia associated with cardiac arrest

Ischemic spinal cord damage from cardiac arrest is rare. A 48-year-old man underwent a straightforward retroperitoneal aortofemoral bypass operation. The following day, he developed cardiac arrest and was resuscitated successfully, but permanent paraplegia was observed soon afterwards.     

Digital arteritis and bleomycin. Apropos of a case

A 47-year-old patient developed severe digital arteritis after complementary bleomycin treatment following surgery for esophageal cancer. Arteriography images showed extrinsic stenosis of the digital arteries, results of other investigations suggesting development of a sclerodermic process due to bleomycin. Ischemic lesions regressed after thoracic sympathectomy. Similar cases have been well documented but cases of associated cancer and digital ischemia lacking iatrogenic features have also been reported. The pathogenic role of bleomycin appears to be established in the present case, but the possibility of the digital ischemia developing within the framework of a paraneoplasic syndrome is discussed.     

胸腹主动脉瘤手术中重建肋间动脉的简易方法

目的:脊髓缺血性损伤是胸腹主动脉瘤手术后一种严重并发症,改进重建肋间动脉的外科技巧可减少这一风险的发生。方法:自2003年8月至2005年1月,行全胸腹主动脉替换术41例(男性30例,女性11例),年龄22～58岁,平均(40.3±9.1)岁。Crawford Ⅱ型38例,Crawford Ⅲ型3例,其中马方综合征合并胸腹主动脉瘤19例。采用深低温、分段停循环技术应用四分叉人工血管行全胸腹主动脉替换,其中自T6-L2肋间和腰动脉开口动脉壁修剪重建成新肋间血管管道,再与四分叉血管之8mm分支吻合,恢复脊髓血供。结果:术后早期死亡3例(病死率7.3%),脑部系统并发症3例(7.9%),脊髓损伤并发症2例(5.3%),均经脱水及神经营养治疗后痊愈。随访除3例死亡(病死率7.9%)外均生存良好,CT检查显示"新肋间动脉"血流通畅。结论:在胸腹主动脉瘤四分叉人工血管置换术中,采用修剪重建新肋间血管管道的方法,能简化手术方式,明显缩短脊髓和重要腹腔脏器的缺血时间,减少脊髓并发症发生,效果良好。     

Milestones in umbilical cord blood transplantation

Much has been learned about umbilical cord blood (UCB) since the first human cord blood transplant was performed back in 1988. Cord blood banks have been established worldwide for the collection, cryopreservation and distribution of UCB for allogeneic haematopoietic stem cell transplantation. UCB has now become one of the most commonly used sources of haematopoietic stem cells for allogeneic transplantation. Today, a global network of cord blood banks and transplant centres has been established with a large common inventory, allowing for more than 20000 transplants worldwide in children and adults with severe haematological diseases. Several studies have been published on UCB transplant, assessing risk factors such as cell dose and human leucocyte antigen mismatch. New strategies are ongoing to facilitate engraftment and reduce transplant-related mortality and include the use of reduced-intensity conditioning regimen, intra-bone injection of cord blood cells, double cord blood transplants or ex vivo expansion of cord blood cells. The absence of ethical concern and the unlimited supply of cells explain the increasing interest of using UCB for developing regenerative medicine.     

New Insights into the Pathophysiology of Detrusor-Sphincter Dyssynergia

Detrusor-sphincter dyssynergia (DSD) is a condition in which the urethral outlet actively contracts during a detrusor contraction. This is most often caused by isolated and complete suprasacral spinal cord lesions and can be manifested by external urethral sphincter (EUS) or bladder neck/proximal urethral smooth muscle contraction, or both, reflexly generated against a hyperreflexive detrusor contraction. The resultant generation of high intravesical pressures, if left untreated, can cause damage to the bladder itself and result in ureteral reflux, hydronephrosis, and renal failure. Current therapies solve some problems but do not address the underlying pathology. Thus, understanding the pathophysiology underlying EUS DSD remains a priority in the urologic care of patients with suprasacral transverse spinal myelopathies. This review examines data and concepts from animals and humans to elucidate the pathophysiology of EUS DSD.     

Ischemic colitis during interferon-ribavirin therapy for chronic hepatitis C: a case report

Ischemic colitis is a rare complication of interferon administration. Only 9 cases in 6 reports have been described to-date. This report describes a case of ischemic colitis during pegylated interferon and ribavirin treatment for chronic hepatitis C, and includes a review of the relevant literature. A 48-year-old woman was treated with pegylated interferon α-2a and ribavirin for chronic hepatitis C, genotype Ib. After 19 wk of treatment, the patient complained of severe afebrile abdominal pain with hematochezia. Vital signs were stable and serum white blood cell count was within the normal range. Abdominal computed tomography showed diffuse colonic wall thickening from the splenic flexure to the proximal sigmoid colon, which is the most vulnerable area for the development of ischemic colitis. Colonoscopy revealed an acute mucosal hyperemic change, with edema and ulcerations extending from the proximal descending colon to the sigmoid colon. Colonic mucosal biopsy revealed acute exudative colitis. Polymerase chain reaction and culture for Mycobacterium tuberculosis were negative and the cultures for cytomegalovirus, Salmonella and Shigella species were negative. After discontinuation of interferon and ribavirin therapy, abdominal pain and hematochezia subsided and, following colonoscopy showed improvement of the mucosal ulcerations. Ischemic colitis cases during interferon therapy in patients with chronic hepatitis C reported so far have all involved the descending colon. Ischemic colitis is a rarely encountered complication of interferon administration in patients with chronic hepatitis C and should be considered when a patient complains of abdominal pain and hematochezia.     

There is More to Life than Revascularization: Therapeutic Targeting of Myocardial Ischemia/Reperfusion Injury

Ischemic heart disease is the world's leading cause of death, and while clinical advances have meant improved and more rapid revascularization, there remains a significant element of myocardial death that thus far has not been successfully targeted in clinical practice, namely lethal reperfusion injury. Ischemia‐reperfusion injury has been the subject of intense research over the last 40 years and our appreciation of the mechanisms of cellular death and salvage have increased immensely over this time, to the extent that a number of clearly identifiable therapeutic targets can now be subjected to clinical trials, as the basic science translates into potentially effective therapies in patients presenting with acute coronary syndromes. In this review, we aim to provide an overview of current evidence regarding the mechanisms of lethal reperfusion injury and endogenous protection, how cardioprotective pharmacological manipulations have been approached to date, and to indicate where therapies may be targeted in the future.     

Current status of umbilical cord blood hematopoietic stem cell transplantation

The number of umbilical cord blood transplants is increasing worldwide. At this time, it is important to evaluate their results and to compare the outcome of umbilical cord blood transplants with allogeneic bone marrow transplants.Data have been reported to the Eurocord Registry by multiple transplant centers. Close links have been established with the cord blood banks through Netcord. Bone marrow transplant data have been provided by transplant centers and through the European Blood and Marrow Transplant (EBMT) and International Bone Marrow Transplant Registries (IBMTR).Eurocord has analyzed the outcomes of 527 umbilical cord blood transplants from 121 transplant centers and 29 countries. The donor was related in 138 cases and unrelated in 399 cases. The results showed that survival with umbilical cord blood transplants was comparable to that with related or unrelated bone marrow transplants. Engraftment with cord blood was delayed resulting in an increased incidence of early transplant complications. The incidence of acute and chronic graft-vs-host disease was reduced with cord blood grafts even in HLA-mismatched transplants and in adults. In patients with leukemia, the rate of relapse was similar to the rate of relapse after bone marrow transplant. The overall event-free survival with umbilical cord blood transplantation was not statistically different compared to bone marrow transplants.This large registry study confirms the potential benefit of using umbilical cord blood hematopoietic stem cells for allogeneic transplants.     

Ten years of cord blood transplantation: from bench to bedside

Cord blood is an unlimited source of haematopoietic stem cells for allogeneic haematopoietic stem cell transplant. Since the first human cord blood transplant, cord blood banks have been established worldwide for collection and cryopreservation of cord blood for allogeneic haematopoietic stem cell transplant. More than 400 000 cord blood units are now available for international exchange. Results of unrelated allogeneic cord blood transplants in malignant and non-malignant diseases, in adults and children, show that, compared to human leucocyte antigen (HLA)-matched unrelated bone marrow transplant, cord blood has several advantages, including prompt availability of the transplant, decrease of graft-versus-host disease and better long-term immune recovery resulting in a similar long term survival. Several studies have shown that the number of cells is the most important factor for engraftment while some degree of HLA mismatches is acceptable. Progress is expected to facilitate engraftment and reduce transplant-related mortality and includes reduced intensity conditioning regimen, intra bone injection of cord blood cells and double cord blood transplants. In addition to haematopoietic stem cells, cord blood and placenta contain a high number of non-haematopoietic stem cells that explains the increasing interest of using cord blood for developing regenerative medicine.     

Left ventricular assist devices: evolving devices and indications for use in ischemic heart disease

PURPOSE OF REVIEW: The mortality with end-stage heart failure is extremely high, especially when patients become refractory to conventional medical therapy and require frequent hospitalization. Ischemic heart disease remains the primary cause of advanced heart failure. Mechanical pumps or devices have been developed called ventricular assist devices and are being used to support an increasing number of patients with refractory heart failure. RECENT FINDINGS: The use of ventricular assist devices has evolved from initially only support of patients unable to be weaned from a heart-lung machine after cardiac surgery to use now as a bridge to a heart transplant, including patients with acute myocardial infarction and shock and severe pulmonary hypertension. More recently, they have been proven as a definitive alternative for patients not eligible for heart transplantation. There are new devices being examined in clinical trials, including a change from pusher-plate to devices with axial flow technology that are much smaller and easier to implant. Outcomes with their use are improving rapidly as the devices become more reliable and more is learned about the importance of candidate selection. SUMMARY: This review describes current indications for the use of these devices, the types of pumps now available, criteria for initiating ventricular assist device support, complications of their use, and new applications such as a platform for stem cell therapy for treatment of end-stage heart failure.     

Epsilon protein kinase C as a potential therapeutic target for the ischemic heart

Ischemic heart disease is the leading cause of morbidity and mortality in the western world. Ischemic damage can occur by acute myocardial infarction, stable angina, cardiac stunning, and myocardial hibernation. In addition, 'scheduled' ischemic events, occurring during cardiac surgery, heart transplantation, and elective angioplasty, can also result in cardiac damage. Ischemic or pharmacological preconditioning can decrease the extent of damage to the myocardium. Although the mechanism of preconditioning-mediated cardioprotection is not fully understood, epsilonPKC has been implicated as a critical mediator of this process in animal studies. The use of isozyme-specific pharmacological tools has permitted a better elucidation of the upstream stimuli and the downstream transducers of epsilonPKC in the pathways leading to cardioprotection. While little is known about the role of epsilonPKC in these pathways in humans, animal studies suggest a potential therapeutic role of epsilonPKC. This review will focus on the role of epsilonPKC in cardiac protection and on the signal transduction cascades that have been implicated in this protection.     

A case of peripheral ischemic complication after terlipressin therapy]

Hepatorenal syndrome is a severe complication of cirrhosis, leading to death in more than 90% of cases in the absence of liver transplantation. Several treatments have been attempted as a bridge to liver transplantation. Among such treatments, terlipressin is a nonselective V1 vasopressin agonist. When comparing with ornipressin, it is known to have a similar vasoconstricting potency, but much less ischemic complication. We report a case of gangrene on toes and necrosis on the infusion site of left hand which developed after the use of terlipressin due to hepatorenal syndrome in a 41-year-old-man with liver cirrhosis. Ischemic complication of terlipressin is rare and there has been no case report in Korea. Although it is rare, we must pay attention to the peripheral ischemic complication of terlipressin.