Autologous peripheral blood stem cell transplantation for Japanese multiple myeloma patients: results of a feasibility study

A feasibility study on high-dose therapy with autologous peripheral blood stem cell transplantation (HDT/PBSCT) was performed in Japanese patients with multiple myeloma (MM). Twenty evaluable patients younger than 65 years old with stage II/III MM were enrolled in this study. Three courses of VAD were used as initial chemotherapy. High-dose etoposide or cyclophosphamide followed by G-CSF was used for PBSCH, and 1.2-89.3 (median 23.4) x 106/kg of CD34+ cells were collected. Single (11 patients) or tandem (9 patients) HDT with melphalan (MEL) 200 mg/m2 or MEL 140 mg/m2 plus TBI 10 Gy were performed. The incidence of grade 4 toxicity (COG) was 10% and treatment-related mortality was 5%. Complete response and tumor reduction of more than 75% were obtained in 4 (21%) and 16 (84%) out of 19 patients, respectively. The actuarial 3-year overall survival (OS) and event-free survival (EFS) after PBSCT/HDT were 65.6% and 22.0%, respectively. The median EFS duration was 18 months. These preliminary results indicated that HDT/PBSCT is feasible for Japanese MM patients. A prospective randomized clinical trial will be required to assess the efficacy.     

磷酸钙骨水泥对股骨颈骨折内固定辅强作用的组织学评价

背景：将磷酸钙骨水泥作为一种内固定辅强材料可提高骨折固定的稳定性．特别是对伴有骨质疏松、骨质较脆弱的骨折可发挥长期良好的固定作用。 目的：从组织学方向分析磷酸钙骨水泥对股骨颈骨折内固定的辅强作用，并同非辅强及聚甲基丙烯酸甲酯辅强进行对比评估。 设计：随机对照、重复观察、开放性实验。 单位：吉林大学第一医院骨科与基本外科，吉林大学基础医学院病理室，日本爱知医科大学整形外科。 材料：实验于1999—01／2004—01在吉林省洮南市医院、吉林大学、日本爱知医科大学完成：选用45只成熟中国绵羊，平均年龄12．5个月，随机分成3组：非辅强组、磷酸钙骨水泥辅强组．聚甲基丙烯酸甲酯辅强组，15只／组：分别于术后3，6，12周取材，每个时间点5只／组。磷酸钙骨水泥由粉剂和固化液组成（粉剂包括75％α-磷酸三钙、18％磷酸四钙、5％磷酸氢钙和2％Hydroxyapatite；固化液包括5％sodium chondroitin sulphate．12％sodium suecinate和83％水），粉液比为3：1。聚甲基丙烯酸甲酯骨水泥包括97．4％methylmethacrylate、2．6％N dimethyl—paratoluidine和hydroquinone。 方法：①将各组绵羊采用pentobarbital sodium静脉麻醉后，进行截骨、钻孔、攻丝和固定：截骨部位均在右股骨颈基底部，用2枚直径4mm松质骨螺钉经大转子下固定。骨水泥则在螺钉拧入前填充。②磷酸钙骨水泥辅强组向孔中注射调配好粉剂和固化液比例的磷酸钙骨水泥，聚甲基丙烯酸甲酯辅强组向孔中注射聚甲基丙烯酸甲酯骨水泥，非辅强组不给予任何材料。③各组标本首先进行最大载荷测试，然后均在40％，70％，90％．100％乙醇中梯度脱水、染色、聚甲基丙烯酸甲酯包埋。最后用锯切片机沿股骨颈方向连续切片，厚度为150～200μm。硬组织切片在接触显微X线照相机上进行拍     

Quantitative assessment of diastolic filling function: A new Doppler echocardiographic method and in vitro validation

The effects of changes in preload and chamber compliance on the transmitral flow pattern was investigated with a fluid dynamics model. A decrease in compliance led to a steepening of the deceleration slope and a shortening of the pressure half-time in both restricted and nonrestricted valves. An increase in the preload led to a longer pressure half-time but did not affect the slope in the restricted valve. However, increased preload led to a shorter pressure half-time and a steeper slope in the nonrestricted valve.A mathematically derived method to measure the net atrioventricular compliance ( ), where v_a and v_t are flow velocities at the mitral anulus and the mitral tip levels) was then proposed. The values obtained by this method showed a strong correlation with true values (r² = 0.89). A possibility of noninvasive quantitative assessment of diastolic filling function was implied.     

Central vascular structures as a characteristic finding of regenerative nodules using hepatobiliary phase gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid-enhanced MRI and arterial dominant phase contrast-enhanced US

Objective

We investigated the characteristic findings of regenerative nodules (RNs) for differentiating early hepatocellular carcinoma (HCC) from high-grade dysplastic nodules (HGDNs) using magnetic resonance imaging (MRI) with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA; EOB-MRI) and contrast-enhanced ultrasonography (CEUS) in patients with chronic liver disease.

Subjects and methods

Pathologically confirmed lesions (100 early HCCs, 7 HGDNs, and 20 RNs with a maximum diameter of more than 1 cm and mean maximal diameters of 15.5, 15.1, and 14.8 mm, respectively) were enrolled in this retrospective study. The signal intensities of these lesions during the hepatobiliary phase of EOB-MRI were investigated, and findings characteristic of RNs using this modality were also evaluated using CEUS.

Results

Ninety-eight of the 100 early HCCs that were hypo-intense (n = 95), iso-intense (n = 2), or hyper-intense (n = 1) and the seven HGDNs that were hypo-intense (n = 6) or hyper-intense (n = 1) during the hepatobiliary phase of EOB-MRI exhibited centripetal vessels during the arterial dominant phase of CEUS, although one early HCC that was hypo-intense exhibited both centrifugal and centripetal vessels. Eighteen of the 20 RNs and one early HCC that were hyper-intense with a small central hypo-intensity and the remaining two RNs that were hyper-intense on EOB-MRI exhibited centrifugal vessels during the arterial dominant phase of CEUS. The small central hypo-intense area corresponded to central vascular structures in the lesion, such as the hepatic artery and portal vein running from the center to the periphery, when viewed using CEUS.

Conclusion

Central vascular structures may be a characteristic finding of RNs when observed during the hepatobiliary phase of EOB-MRI and the arterial dominant phase of CEUS.

     

An improved method for transseptal left ventricular catheterization

It is difficult to perform a retrograde left ventricular catheterization in patients having an aortic valve replacement. An improvement of the conventional transseptal catheterization (Brockenbrough method) led to a better success rate of catheterization. The fulcrum of the improved catheter was located 7 cm from the tip. Its curvature was approximately 270°. Its tip was bent inward to form a pig-tail shape to prevent myocardial injury. This catheterization was performed 33 times in 32 patients. A 97% success rate was achieved. An exercise loading test was performed with a bicycle ergometer while this catheter was maintained in the left ventricle of a patient placed in a supine position. The catheter was well retained in the left ventricle and produced a minimal number of arrhythmias during exercise. The modification of this catheter has proved to be a better method of left ventricular catheterization in patients with an aortic valve replacement.     

OK-432 pleurodesis for the treatment of pneumothorax in patients with interstitial pneumonia

Background

Pneumothorax occasionally develops in patients with interstitial pneumonia (IP) and is often intractable. As there exists no well-established treatment for pneumothorax with IP, we evaluated the efficacy and safety of pleurodesis with OK-432, a lyophilized preparation of Streptococcus pyogenes Su strain that has been inactivated by benzylpenicillin.

A patient with symptomatic osteomalacia associated with Fanconi syndrome

We report a patient with renal tubulointerstitial fibrosis and symptomatic osteomalacia associated with Fanconi syndrome. A 55-year-old woman was hospitalized because of an inability to walk. Beginning approximately 2 years previously, she had experienced gradually worsening pain in the hips, shoulders, and trunk, culminating in a bedridden state. Serum urea nitrogen was 38 mg/dl; creatinine, 2.6 mg/dl; uric acid. 3.6 mg/dl; phosphate, 2.3 mg/dl; and alkaline phosphatase, 2111 IU/l. Urinary β2 microglobulin was 72 331 µg/day. Aminoaciduria, renal glucosuria, and proximal renal tubular acidosis with a normal anion gap were also noted. The patient was diagnosed with Fanconi syndrome. Radiography demonstrated typical Looser zones in the proximal portion of the left and especially the right femoral shaft, and at several other sites. A renal biopsy specimen disclosed severe tubulointerstitial fibrosis with little cellular infiltration. Glomeruli were largely intact. A bone biopsy specimen indicated osteomalacia; no tetracycline labeling could be seen along most trabecular bone surfaces, and the ratio of total osteoid volume to bone volume was increased (71.8%). Bicarbonate administration (9 g/day) gradually lessened most symptoms, permitting ambulation. Calcitriol administration decreased excessive intact-parathyroid hormone emerging after 2 months of acidosis correction. Thus, severe acidosis associated with Fanconi syndrome can induce osteomalacia showing serious skeletal complications, but also responsiveness to bicarbonate therapy.     

Chinese herbs and bone disease

We treated a patient with an unusual bone disease at least partly associated with Chinese herbs. Seven years after 65-year-old man had begun to consume Chinese herbs, multifocal osteoarthralgias were noted, and the patient was hospitalized for renal dysfunction (serum creatinine, 2.8 mg/dl; urea nitrogen, 19 mg/dl). Fanconi syndrome also was apparent. A renal biopsy specimen showed tubulo-interstitial fibrosis. Chinese herbs were discontinued and prednisolone was started, but bone and joint pain as well as renal function gradually worsened. Four years later, creatinine was 9.0 mg/dl and alkaline phosphatase was 571 IU/l. As bone scintigraphy revealed localized asymmetric lesions, Paget's disease of bone was suspected at first. However, neither osteosclerosis nor hypertrophy was seen in radiographs. Based on a bone specimen histology we diagnosed as mixed-type renal osteodystrophy including osteomalacia and osteitis fibrosa. Mosaic pattern of cement lines was not present. This case was not compatible with either Paget's disease or typical renal osteodystrophy as seen in dialysis patients. Etidronate disodium was effective in alleviating bone symptoms. The patient's bone disorder may be a new disease at least partly related to Chinese herbs independently of nephropathy.     

Transfer of human serum IgG to nonobese diabetic Igμnull mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjögren’s syndrome

The NOD (nonobese diabetic) mouse has been studied as an animal model for autoimmune insulin-dependent diabetes and Sjögren’s syndrome. NOD.Igμ^null mice, which lack functional B lymphocytes, develop progressive histopathologic lesions of the submandibular and lachrymal glands similar to NOD mice, but in the absence of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in salivary and lachrymal tissues, NOD.Igμ^null mice fail to lose secretory function as determined by stimulation of the muscarinic/cholinergic receptor by the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating exocrine dryness. Infusion of purified serum IgG or F(ab′)₂ fragments from parental NOD mice or human primary Sjögren’s syndrome patients, but not serum IgG from healthy controls, alters stimulated saliva production, an observation consistent with antibody binding to neural receptors. Furthermore, human patient IgG fractions competitively inhibited the binding of the muscarinic receptor agonist, [³H]quinuclidinyl benzilate, to salivary gland membranes. This autoantibody activity is lost after preadsorption with intact salivary cells. These findings indicate that autoantibodies play an important part in the functional impairment of secretory processes seen in connection with the autoimmune exocrinopathy of Sjögren’s syndrome.