Clinical-genetic characteristics and treatment outcomes of Turkish children with Gaucher disease type 1 and type 3: A sixteen year single-center experience

Data from 38 children were retrospectively analyzed to determine the patient characteristics of Turkish children with Gaucher disease (GD) and evaluate the impact of enzyme replacement therapy (ERT) in a pediatric cohort consisting of two different sub-types of the disease, Gaucher disease type 1 (GD1) and type 3 (GD3). Both types were represented equally (GD1/GD3 = 20/18). L444P (35.5%) was the most common mutant allele while L444P/L444P (34.2%) was the most common genotype overall. Compound heterozygosity of N370S and L444P homozygosity were the dominant genotypes in Turkish children with GD1 and GD3, respectively. None of the patients had moderate to severe thrombocytopenia at last follow-up while the percent of patients with anemia decreased from 60% to 5.7% (p < 0.001). Significant improvements in mean liver (from 2.2 to 1.6 MN, p < 0.001) and spleen (from 15.5 to 7.6 MN, p < 0.001) volumes were observed in the first year of ERT. Linear growth was ameliorated as shown by the decrease in the percent of patients having short stature from 34.3% to 13.3% (p < 0.01) at year 5. Erlenmeyer flask deformity, osteopenia and scoliosis were common skeletal findings. Although none of the patients had lung disease at diagnosis, 20% developed radiological findings suggestive of pulmonary involvement. This single center experience is the first comprehensive study from Turkey not only reporting clinical and genetic characteristics of GD patients but also providing information on the outcomes of ERT in two different sub-types of GD. Genotypic background of Turkish children with GD is similar to western populations. Although visceral and hematological therapeutic goals are reached as early as one year of ERT in both sub-types, achieving normal growth takes several more years than suggested in significant number of children with GD.     

Hyperglycemic hyperosmolar syndrome caused by steroid therapy in a patient with lupus nephritis

A 51-yr-old female was referred to our outpatient clinic for the evaluation of generalized edema. She had been diagnosed with idiopathic thrombocytopenic purpura (ITP). She had taken no medicine. Except for the ITP, she had no history of systemic disease. She was diagnosed with systemic lupus erythematosus. Immunosuppressions consisting of high-dose steroid were started. When preparing the patient for discharge, a generalized myoclonic seizure occurred at the 47th day of admission. At that time, the laboratory and neurology studies showed hyperglycemic hyperosmolar syndrome. Brain MRI and EEG showed brain atrophy without other lesion. The seizure stopped after the blood sugar and serum osmolarity declined below the upper normal limit. The patient became asymptomatic and she was discharged 10 weeks after admission under maintenance therapy with prednisolone, insulin glargine and nateglinide. The patient remained asymptomatic under maintenance therapy with deflazacort and without insulin or medication for blood sugar control.     

PF-LCP与PFNA治疗高龄股骨粗隆间骨折Evans III-V型临床对比研究

目的 探讨PF-LCP与PFNA治疗高龄股骨粗隆间骨折Evans III-V型临床疗效及安全性差异。方法 研究对象选取我院2012年4月~2015年4月收治Evans III-V型高龄股骨粗隆间骨折共110例,以随机区组法分为A组（55例）和B组（55例）,分别采用PF-LCP与PFNA术式治疗;比较两组患者围手术期临床指标水平、术后随访髋关节Harris评分及术后并发症发生率等。结果 B组患者手术时间和术中失血量均显著优于A组,差异具有显著性意义（P<0.05）;两组患者骨折愈合时间和住院时间比较差异无统计学意义（P>0.05）;B组患者术后随访Harris评分显著高于A组,差异具有显著性意义（P<0.05）;B组患者术后并发症发生率显著低于A组,差异具有显著性意义（P<0.05）。结论 PFNA治疗高龄股骨粗隆间骨折Evans III-V型可有效缩短手术时间,减少术中创伤,改善术后髋关节功能,且有助于降低术后并发症发生风险,价值优于PF-LCP。     

低剂量利妥昔单抗治疗温抗体型自身免疫性溶血性贫血的系统评价

目的标准剂量利妥昔单抗(RTX)(375 mg/m2/周×4)已成为难治复发温抗体型自身免疫性溶血性贫血(w AIHA)的首选二线治疗。尽管如此,低剂量RTX治疗w AIHA的疗效仍值得探讨。方法通过对PUBMED数据库和CNKI数据库的文献检索,本研究共纳入13项临床研究,对172例患者进行系统评价。结果低剂量RTX(100 mg/周×4)治疗w AIHA总反应率达到87.8%,其中完全缓解(CR)率62.8%,部分缓解(PR)率25%。由于病例数少,各组报道复发率差异较大,从0~62.5%不等,复发后再治疗仍有有效病例报道。无严重不良反应。结论低剂量RTX治疗w AIHA安全有效,不良反应少。     

A case of autoimmune hemolytic anemia associated with an ovarian teratoma

Autoimmune hemolytic anemia associated with an ovarian teratoma is a very rare disease. However, treating teratoma is the only method to cure the hemolytic anemia, so it is necessary to include ovarian teratoma in the differential diagnosis of autoimmune hemolytic anemia. We report herein on a case of a young adult patient who had severe autoimmune hemolytic anemia that was induced by an ovarian teratoma. A 25-yr-old woman complained of general weakness and dizziness for 1 week. The hemoglobin level was 4.2 g/dL, and the direct and indirect antiglobulin tests were all positive. The abdominal computed tomography scan revealed a huge left ovarian mass, and this indicated a teratoma. She was refractory to corticosteroid therapy; however, after surgical resection of the ovarian mass, the hemoglobin level and the reticulocyte count were gradually normalized. The mass was well encapsulated and contained hair and teeth. She was diagnosed as having autoimmune hemolytic anemia associated with an ovarian teratoma. To the best of our knowledge, this is the first such a case to be reported in Korea.     

Challenges in management of atypical hemolytic uremic syndrome: Bottle neck in resource limited settings

Treatment of atypical hemolytic uremic syndrome cases is challenging right from establishing correct and timely diagnosis to execution of management protocol. A seven-year-old male child from poor socioeconomic status was admitted with chief complaints of fever, 3 episodes of vomiting and passage of cola coloured urine. Based on clinical and laboratory findings, diagnosis was established. However, ADAMTS13 levels and genetic studies required for diagnosis could not be performed due to financial constraints and non-availability of these tests. TPE kits were arranged from charitable organizations. Six TPE procedures were performed using Cobe Spectra cell separator. Central venous catheter was placed in femoral vein. TPE kit was primed with compatible packed red blood cells before each procedure. Patient was non-cooperative and irritable in first three procedures and was sedated. A total of 1300 ml plasma was exchanged in each procedure with group specific fresh frozen plasma. After second TPE procedure, patient started improving with decrease in plasma discoloration and periorbital edema. Renal function tests along with hematological parameters became normal after 6th TPE procedure. Patient was discharged in a stable condition. On follow up, C3 levels were normal with adequate platelet count and normal renal functions suggesting complete remission.     

Relation between anemia and vulnerable coronary plaque components in patients with acute coronary syndrome: virtual histology-intravascular ultrasound analysis

The aim of the present study was to evaluate the plaque components and the predictors of thin-cap fibroatheroma (TCFA) in anemic patients with acute coronary syndrome using virtual histology-intravascular ultrasound (VH-IVUS). Anemia was defined according to criteria of the World Health Organization, (i.e. , hemoglobin levels < 13 g/dL in men and < 12 g/dL in women) and we compared VH-IVUS findings between anemia group (171 patients, 260 lesions) and non-anemia group (569 patients, 881 lesions). Anemia group had greater % necrotic core (NC) volume (21% ± 9% vs 19% ± 9%, P = 0.001) compared with non-anemia group. Hemoglobin level correlated negatively with absolute NC volume (r = -0.235, P < 0.001) and %NC volume (r = -0.209, P < 0.001). Independent predictors of TCFA by multivariate analysis were diabetes mellitus (odds ratio [OR], 2.213; 95% confidence interval [CI], 1.403-3.612, P = 0.006), high-sensitivity C-reactive protein (OR, 1.143; 95% CI, 1.058-1.304, P = 0.012), microalbuminuria (albumin levels of 30 to 300 mg/g of creatinine) (OR, 2.124; 95% CI, 1.041-3.214, P = 0.018), and anemia (OR: 2.112; 95% CI 1.022-3.208, P = 0.028). VH-IVUS analysis demonstrates that anemia at the time of clinical presentation is associated with vulnerable plaque component in patients with acute coronary syndrome.     

Successful treatment of refractory thrombocytopenia with mycophenolate mofetil in a patient with systemic lupus erythematosus

While mild thrombocytopenia in systemic lupus erythematosus (SLE) is frequently seen in the context of active disease, severe thrombocytopenia causing significant bleeding is not that common. Corticosteroids are considered the first line therapy for severe thrombocytopenia in SLE. Second-line therapeutic agents or splenectomy have been reported to be effective for patients who fail to respond to steroids or those who require moderate doses of steroids to maintain the platelet counts. Recent randomized controlled studies have shown that mycophenolate mofetil (MMF) is an efficacious and safe therapeutic agent in patients with proliferative forms of lupus nephritis. However, little information has been available regarding the role of MMF in the treatment of immune thrombocytopenia complicated with SLE. Hereby I describe a patient with SLE in whom thrombocytopenia was refractory to corticosteroids, intermittent intravenous cyclophosphamide, azathioprine, cyclosporine, intravenous gamma globulin, danazol, and splenectomy, and whose platelet counts eventually normalized during therapy with MMF. In this patient, thrombocytopenia is initially thought to be associated with active SLE involving major organ. However, after immunosuppressive agents were given, the refractory nature of thrombocytopenia seems to be an isolated phenomenon, independently of SLE activity.     

A case of a patient with both chorea and restless legs syndrome

The patient was a 44-yr-old man with end-stage renal disease who had developed chorea as a result of hypoglycemic injury to the basal ganglia and thalamus and who was subsequently diagnosed with depression and restless legs syndrome (RLS). For proper management, the presence of a complex medical condition including two contrasting diseases, chorea and RLS, had to be considered. Tramadol improved the pain and dysesthetic restlessness in his feet and legs, and this was gradually followed by improvements in his depressed mood, insomnia, lethargy, and feelings of hopelessness. This case suggests that the dopaminergic system participates intricately with the opioid, serotoninergic, and noradrenergic systems in the pathophysiology of RLS and pain and indirectly of depression and insomnia.     

Evans截骨跟骨外侧柱延长副舟骨切除胫后肌腱重建治疗副舟骨源性平足症的临床疗效观察

目的探讨Evans截骨联合胫后肌腱止点重建治疗伴前足外展副舟骨源性平足症的方法及临床疗效。方法 2013年9月~2016年9月,对20例(25足)经半年以上保守治疗疗效欠佳的伴前足外展副舟骨源性平足症患者采用Evans截骨联合胫后肌腱止点重建治疗。应用美国矫形足踝协会(AOFAS)评分标准及VAS疼痛评分评估治疗效果,同时对比术前和终末随访的足弓高度、跟骨倾斜角、前后位跟距角、侧位跟距角、前后位距骨-第1跖骨角、侧位距骨-第1跖骨角、距舟覆盖角等X片评价指标。结果术后患者切口均Ⅰ期愈合,无相关并发症发生。跟骨外侧柱延长植骨愈合。术后20例(25足)患者获随访,随访时间6~20个月,平均12个月。末次随访时中足功能AOFAS评分、VAS疼痛评分、足弓高度、跟骨倾斜角、侧位跟距角、前后位跟距角、侧位距骨-第1跖骨角、前后位距骨-第1跖骨角、距舟覆盖角等X片评价指标与术前比较,差异均有统计学意义(P0.05)。结论采用Evans截骨联合胫后肌腱止点重建治疗伴前足外展副舟骨源性平足症可有效纠正畸形,减轻疼痛,恢复功能。     

Genetic analysis of three Korean patients with clinical features of Ehlers-Danlos syndrome type IV

Ehlers-Danlos syndrome (EDS) is a hereditary disorder of the connective tissue. EDS type IV (EDS IV), the vascular type of the disease, is characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations in the gene for type III procollagen (COL3A1). However, recent studies suggest that the causative mutation of EDS IV is not homogeneous. We report our experience with three patients presenting with clinical features of type IV EDS. A 48-yr-old woman presented with acute aortic dissection (patient 1) and 36-yr-old and 21-yr-old women presented with carotidcavernous fistula (patients 2 and 3, respectively). All three patients bruised easily. Two patients (patients 1 and 3) had thin transparent skin with visible veins. Genetic analysis of COL3A1 revealed a Gly732Val (c.2195G>T) mutation in patient 1 and a duplication of 15 base pairs (c.3221_3235dup) which resulted in an interposition of five amino acids (p.Gly1074_Pro1078dup) in patient 2. However, no mutations were observed in COL3A1 or transforming growth factor beta receptors 1 and 2 in patients 3, which might be either due to a deletion of single or multiple exons in the COL3A1 gene or due to a genetic heterogeneity. This is the first report of genetically confirmed cases of EDS IV in Korea.     

A further patient with the lethal type of Larsen syndrome.

We present a female infant with multiple joint dislocations, flat facies, cleft soft palate, redundant neck skin, pulmonary hypoplasia, and skeletal abnormalities.     

Association of serum 25-hydroxyvitamin D levels with markers for metabolic syndrome in the elderly: a repeated measure analysis

The purpose of current study was to investigate associations of serum 25-hydroxyvitamin D (OHVD) levels with markers for metabolic syndrome in elderly Koreans. We conducted a panel study on 301 individuals over 60 yr old in Seoul, Korea, and repeatedly measured serum OHVD, glucose, insulin, and lipid levels. Mixed effect model and generalized estimating equations were used to investigate relationships between serum OHVD levels with marker levels for metabolic syndrome and each of its categories. Of all subjects, 76.6% were vitamin D deficient (< 50 nM) and 16.9% were insufficient (< 75 nM). Inverse association was demonstrated between serum OHVD levels and insulin (P = 0.004), triglyceride (P = 0.023) and blood pressure (systolic blood pressure: P = 0.002; diastolic blood pressure: P < 0.001). Vitamin D deficiency was found to increase risk of 'hypertriglyceridemia' category of metabolic syndrome (odds ratio: 1.73, 95% confidence interval: 1.13-2.66). In conclusion, we found from our repeated measure analysis that decreasing serum OHVD levels are associated with increasing insulin resistance, increasing serum triglyceride levels and increasing blood pressure in elderly Koreans, and confirmed on the risk of 'hypertriglyceridemia' in vitamin D deficient subjects.     

Atypical type III hyperlipoproteinemia in a patient with Ig A myelomatosis

Summary We studied a 58-year-old woman with severe therapy-refractory hyperlipidemia, xanthomatosis, and multiple myeloma (immunoglobulin A, lambda light chain). The lipid disorder became evident about half a year prior to the expression of myelomatosis. Clinical symptoms were similar to those found in classical type III hyperlipoproteinemia but the underlying metabolic defect was different from the one described in this primary dyslipoproteinemia. The patient has the heterozygous apolipoprotein E3/2 phenotype and her VLDL-cholesterol/serum-triglyceride ratio is unusually low at 0.05. Evidence is given that the hyperlipoproteinemia is due to an impaired catabolism of intermediate density lipoproteins probably because of a reduced hepatic triglyceride lipase activity.Abbreviations AIH autoimmune hyperlipidemia - Chol cholesterol - HDL high density lipoproteins - HLP hyperlipoproteinemia - HTGL hepatic triglyceride lipase - IDL intermediate density lipoproteins - IEF isoelectric focusing - Ig immunoglobulin - LDL low density lipoproteins - LPL lipoprotein lipase - PL phospholipids - TG triglycerides - VLDL very low density lipoproteins     

Effect of zoledronic acid on acro-osteolysis and osteoporosis in a patient with Hajdu-Cheney syndrome

Hajdu-Cheney syndrome is a rare, autosomal dominant skeletal dysplasia marked by acro-osteolysis of the distal phalanges and severe osteoporosis. Although there are more than 60 reports published to date, proper treatment and subsequent outcome have been scarce. Herein, we report a progress of anti-resorptive therapy with zoledronic acid, in a woman with Hajdu-Cheney syndrome. Results suggest that anti-resorptive therapy may be important in delaying the progress of osteoporosis and preventing fractures, but not necessarily acro-osteolysis itself.     

Treatment with rituximab in patients with mixed cryoglobulinemia syndrome: results of multicenter cohort study and review of the literature

Objective

Mixed cryoglobulinemia syndrome (MCs) is a systemic vasculitis characterized by multiple organ involvement due to the vascular deposition of immune-complexes, mainly the cryoglobulins. B-lymphocyte expansion represents the underlying pathological alteration frequently triggered by hepatitis C virus (HCV) infection. The treatment of MCs syndrome is generally based on antiviral drugs and/or immunosuppressors, among which rituximab, an anti-CD20 monoclonal antibody, has been usefully employed for both cutaneous and visceral MCs organ involvement. This multicenter study retrospectively evaluated the effects of rituximab in a large series of patients with active MCs. The observed results were compared to those emerging from the updated review of the literature on this topic.

Methods

The study included 87 patients (male/female 19/68, mean age 62.3 ± 11.4SD years, mean disease duration 9 ± 6.2SD years, HCV infection in 92% of cases) with active cryoglobulinemic vasculitis evaluated before rituximab monotherapy and after 6-month follow-up by means of main clinico-serological parameters. A PubMed search up to May 31, 2011, was done to find published clinical studies, including case reports of MCs treated with rituximab.

Results

A significant clinical improvement was observed in a relevant percentage of cases, regardless the presence/absence of associated HCV infection; namely, complete/partial remission of pre-treatment active manifestations was observed in 74% of skin purpuric lesions, up to 87% of non-healing vasculitic leg ulcers, and 44% of the peripheral neuropathy, mainly paresthesias (patient's visual analogical scale from 62 ± 25 to 37 ± 27; p ≤ .0001). Moreover, cryoglobulinemic nephropathy, observed in 38 patients, significantly improved in 95% of cases (serum creatinine from 1.8 ± 1.1SD to 1.4 ± 0.8SD mg/dl, p ≤ .0001; 24-hour proteinuria from 2.2 ± 2.1SD to 0.9 ± 1.7SD g/24 h, p ≤ .0001), with complete remission in the 50%. Among 6 patients with complicating non-Hodgkin's B-cell lymphoma a complete or partial remission was observed in 5/6. A complete remission of abdominal vasculitis was also observed in one patient. These beneficial effects were mirrored by the improvement of cryoglobulinemic serological hallmarks, namely cryocrit and low complement C4, in half cases.The safety of rituximab was confirmed by the small number of side effects recorded during the 6-month follow-up.On the whole, the results of the present study are in keeping with those reported in 39 papers present in world literature, including a total of 279 MCs patients.

Conclusions

Rituximab may be regarded as useful and safe pathogenetic treatment of cryoglobulinemic vasculitis. The actual role of this drug should be definitely confirmed by randomized controlled trials, as well as its position in the therapeutical strategy, mainly with respect to antiviral treatment in HCV-associated MCs.     

膝关节正中切口双钢板固定治疗股骨远端C2、C3型骨折疗效分析

目的比较外侧钢板与双钢板内固定治疗股骨远端C2、C3型骨折的临床疗效,探讨双钢板固定治疗股骨远端C2、C3型骨折的可行性和疗效优势。方法回顾性分析2012年1月至2017年6月手术治疗股骨远端C2、C3型骨折38例,其中17例采用膝关节正中切口双钢板固定,21例采用传统外侧钢板固定,患者术后均采用主动运动,并结合练习器辅助持续被动活动,以促进膝关节的功能恢复。依据Hohl临床评分标准比较两组股骨远端C2、C3型骨折患者术后6周、6个月的膝关节功能。结果术后随访10~36个月(平均20.5个月),依据Hohl标准对股骨远端C2、C3型骨折疗效进行临床评分,膝关节正中切口双钢板固定组的术后6周膝关节功能评定结果为:优12例,良3例,中1例,差1例;外侧钢板固定组为:优9例,良5例,中4例,差3例。两组的优良率分别为88.24%和66.67%,差异有统计学意义。膝关节正中切口双钢板固定组发生2例延迟愈合,外侧钢板固定组有4例延迟愈合,含1例骨不连经二次手术后愈合,两组均无骨关节感染及下肢深静脉血栓形成。结论膝关节正中切口双钢板固定法治疗股骨远端C2、C3型骨折能够解决单钢板固定偏心性固定不稳的问题,方法可行,内固定强度可靠,通过早期锻炼,相较单钢板固定在早期膝关节功能恢复方面更有优势,且并发症少。     

A case of reactive plasmacytosis mimicking multiple myeloma in a patient with primary Sjogren's syndrome

Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease with well-documented association of lymphoid malignancies during the progress of the disease. Although several types of malignancy and pseudomalignancy have been reported in pSS, low-grade non-Hodgkin's lymphomas are the most frequently observed. Reactive plasmacytosis mimicking myeloma is a very rare condition in association with pSS. We describe a 72-yr-old woman with pSS who presented with hypergammaglobulinemia, and extensive bone marrow and lymph node plasmacytosis, which mimicked multiple myeloma. In this patient, there was an abnormal differentiation of memory B cells to plasma cells in the peripheral blood suggesting underlying pathogenetic mechanism for this condition.     

Aerobic exercise training induces metabolic benefits in rats with metabolic syndrome independent of dietary changes

OBJECTIVES:

We evaluated the effects of aerobic exercise training without dietary changes on cardiovascular and metabolic variables and on the expression of glucose transporter Type 4 in rats with metabolic syndrome.

METHODS:

Twenty male spontaneously hypertensive rats received monosodium glutamate during the neonatal period. The animals were allocated to the following groups: MS (sedentary metabolic syndrome), MS-T (trained on a treadmill for 1 hour/day, 5 days/week for 10 weeks), H (sedentary spontaneously hypertensive rats) and H-T (trained spontaneously hypertensive rats). The Lee index, blood pressure (tail-cuff system), insulin sensitivity (insulin tolerance test) and functional capacity were evaluated before and after 10 weeks of training. Glucose transporter Type 4 expression was analyzed using Western blotting. The data were compared using analysis of variance (ANOVA) (p<0.05).

RESULTS:

At baseline, the MS rats exhibited lower insulin sensitivity and increased Lee index compared with the H rats. Training decreased the body weight and Lee index of the MS rats (MS-T vs. MS), but not of the H rats (H-T vs. H). There were no differences in food intake between the groups. At the end of the experiments, the systolic blood pressure was lower in the two trained groups than in their sedentary controls. Whole-body insulin sensitivity increased in the trained groups. Glucose transporter Type 4 content increased in the heart, white adipose tissue and gastrocnemius muscle of the trained groups relative to their respective untrained groups.

CONCLUSION:

In conclusion, the present study shows that an isolated aerobic exercise training intervention is an efficient means of improving several components of metabolic syndrome, that is, training reduces obesity and hypertension and increases insulin sensitivity.     

硼替佐米联合利妥昔单抗和血浆置换治疗高致敏等待肾移植患者

背景：高致敏是肾移植成功的障碍,目前肾移植脱敏治疗方法有静注免疫球蛋白、血浆置换、兔抗人淋巴细胞球蛋白等,但治疗效果常不满意。 目的：通过利妥昔单抗和硼替佐米进行肾移植后脱敏治疗,寻求效果满意的治疗方案。 方法：1例高致敏等待肾移植患者接受脱敏治疗,接受血浆置换2次后,立即给予利妥昔单抗500 mg静滴,2 d后开始分别在第1,4,8,11 天给予硼替佐米1.3 mg/m2,随访观察群体反应性抗体等变化。 结果与结论：随访的9个月中,患者群体反应性抗体从92%下降到17%,患者对利妥昔单抗和硼替佐米有良好的耐受性。初步经验表明：硼替佐米联合利妥昔单抗和血浆置换三联脱敏治疗方案可快速持久降低循环抗体水平,硼替佐米可能成为脱敏治疗方案中的重要要素。