Fludarabine in combination with cyclophosphamide decreases incidence of GVHD and maintains effective graft-versus-leukemia effect after allogeneic stem cell transplantation in murine lymphocytic leukemia

Graft-versus-host disease (GVHD) is a severe disorder and despite therapeutic efforts to decrease its distressing clinical manifestations, treatment is still not optimal. Here we report the results of studies, in which the purine analogue, fludarabine phosphate, was used in an attempt to modify and decrease GVHD after stem cell transplantation, across major histocompatibility barriers for murine leukemia. B-cell leukemia (BCL-1) bearing (BALB/c x C57BL/6) F1 mice received two cycles of fludarabine (0.8 mg/kg) for 5 days every 2 weeks, followed by 400 mg/kg cyclophosphamide i.p. Animals were then transplanted with C57BL/6 precursor cells and the development of leukemia and extent of GVHD was monitored both clinically and histopathologically. In the fludarabine-treated group, only nine of 28 (32%) mice developed leukemia, compared to 25 of 33 (76%) of control animals (P=0.0006 ). Mice treated with fludarabine-containing regimens prior to transplantation also had much less GVHD both clinically and at autopsy, while graft-versus-leukemia appeared to be augmented in the same animals.     

Rhinolalia as a presenting sign of pneumomediastinum complicating post peripheral blood stem cell transplantation bronchiolitis obliterans

A 26-year-old male with graft vs. host disease (GVHD) presented with rhinolalia (a squeaky voice of nasal quality) as a presenting sign for pneumonasopharynx and pneumomediastinum secondary to bronchiolitis obliterans. The patient underwent HLA-identical related peripheral blood stem cells transplantation 8 months before the diagnosis. Three weeks after transplantation he began to suffer from GVHD Grade III that involved the gut, liver, and skin and later on the lungs. Due to severe obstructive bronchiolitis obliterans the patient developed intensive cough evolving into pneumomediastinum and pneumonasopharynx with rhinolalia. The patient was treated conservatively with complete resolution. Although rare, pneumomediastinum and pneumonasopharynx can be a life-threatening event, and one should be aware of the signs and symptoms on physical examination, which may be as subtle as rhinolalia alone.     

Scientific Basis of Botanical Medicine as Alternative Remedies for Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder that causes permanent disability and mortality to approximately 1 to 100 people in the world. Patients with RA not only suffer from pain, stiffness, swelling, and loss of function in their joints, but also have a higher risk of cardiovascular disease and lymphoma. Typically prescribed medications, including pain-relieving drugs, nonsteroidal anti-inflammatory drugs (NSAID), and disease-modifying antirheumatic drugs, can help to relieve pain, reduce inflammation and slow the course of disease progression in RA patients. However, the general effectiveness of the drugs has been far from satisfactory. Other therapeutic modalities like TNF-alpha (TNF-α) inhibitors and interleukin-1 receptor antagonists targeting precise pathways within the immune system are expensive and may be associated with serious side effects. Recently, botanical medicines have become popular as alternative remedies as they are believed to be efficacious, safe and have over a thousand years experience in treating patients. In this review, we will summarize recent evidence for pharmacological effects of herbs including Black cohosh, Angelica sinensis, Licorice, Tripterygium wilfordii, Centella asiatica, and Urtica dioica. Scientific research has demonstrated that these herbs have strong anti-inflammatory and anti-arthritic effects. A wide range of phytochemicals including phenolic acids, phenylpropanoid ester, triterpene glycosides, phthalide, flavonoids, triterpenoid saponin, diterpene and triterpene have been isolated and demonstrated to be responsible for the biological effects of the herbs. Understanding the mechanisms of action of the herbs may provide new treatment opportunities for RA patients.     

Primary hepatic neuroendocrine tumor: Five cases with different preoperative diagnoses

Neuroendocrine tumors, also known as carcinoid tumors, behave like benign tumors; however, they show the characteristics of carcinoma. While more than 80% of the neuroendocrine tumors found in the liver are metastatic, primary hepatic neuroendocrine tumors are very rare. Five patients with hepatic mass who admitted to our clinic between August 2003 and July 2007 were treated surgically. Ultrasonography, computerized tomography and magnetic resonance imaging were performed in all patients. Endoscopy and colonoscopy were conducted to exclude malignancy of other sites. Hepatectomy was carried out in all patients. Diagnosis was confirmed with immunohistochemical examination. The five patients treated surgically were diagnosed as primary hepatic neuroendocrine tumor histopathologically. Abdominal pain was the most common complaint of all patients. Hepatectomy was conducted in all patients due to tumors originating from the liver lobes. Only one patient (Case 2) underwent transarterial chemoembolization before hepatectomy to reduce tumor bleeding. Owing to tumor recurrence on the left lobe of the liver in Case 2, transarterial chemoembolization was performed four years after hepatectomy. R0 resection was achieved in two patients (Cases 1 and 3). In conclusion, primary hepatic neuroendocrine tumors are very rare and asymptomatic tumors. Thus, high-sensitive laboratory and imaging examinations are required. At present, hepatectomy remains the main treatment for primary hepatic neuroendocrine tumor.     

Influence of Ankaferd Blood Stopper on shear bond strength of bonding systems

This study investigated the effect of Ankaferd Blood Stopper (ABS) contamination on bond strength of total- and self-etching systems. Seventy mandibular third molars sectioned in a mesio-distal direction were mounted in acrylic resin, and flat dentin surfaces were exposed. The specimens were randomly assigned to seven groups (n=20), according to the surface treatment: Group I, ABS contamination+37% phosphoric acid+Solobond M; Group II, ABS contamination+Clearfil SE Bond; Group III, ABS contamination+All Bond SE; Group VI, 37% phosphoric acid+ABS contamination+Solobond M; Group V, Solobond M; Group VI, Clearfil SE Bond; and Group VII, All Bond SE. Next, a resin composite (Grandio) was built up using a plastic apparatus and polymerized. The specimens were tested in shear mode at a crosshead speed of 1 mm/min. There were significant differences in bond strengths between the control and ABS-contaminated samples. These findings suggest that ABS contamination reduced bond strength of total- and self-etching adhesives.     

Are they too old? Surgical treatment for metastatic epidural spinal cord compression in patients aged 65 years and older

Abstract

Objectives:

We aimed to assess the efficacy of surgical decompression of metastatic epidural spinal cord compression (MESCC) in patients ≧65 years and review our multidisciplinary surgical decision-making process.

Methods:

We identified all patients operated for MESCC from August 2008 to June 2012. Patients ≧65 years, with a single area of cord compression, back/radicular pain, neurological signs of cord compression, surgery within 48 hours after onset of MESCC-related paraplegia, and follow-up for ≧1 year or until death were included. Files were reviewed retrospectively. The requirement for informed consent was waived. Neurological status was assessed with the American Spinal Injury Association (ASIA) Impairment Scale (AIS). Duration of ambulation and survival were assessed with Kaplan–Meier and Cox regression analysis.

Results:

Twenty-one patients met inclusion criteria (11 women/10 men; mean age 73 years, range 65–87). All presented with debilitating back/neck pain. Ten patients (48%) were not ambulatory before surgery and four suffered urinary incontinence/constipation (19%). Preoperative AIS was E in 5 patients (24%), D in 11 (62%), and C in 5 (24%). Motor symptoms had been present for a mean of 3·8 days (range 1–14). All patients regained ambulation. Overall, mean survival was 320 days (range 19–798) and mean ambulation was 302 days (range 18–747). On 31 March 2013, 7 patients (33%) were alive and ambulatory at a mean of 459 days (range 302–747); 14 patients had died (67%) at a mean of 251 days (range 19–798), with a mean ambulation of 223 days (range 18–730).

Discussion:

With careful patient selection, surgery may achieve long duration of ambulation in patients ≧65 years with MESCC.     

Normalization of serum lactic dehydrogenase in β-thalassemia patients following bone marrow transplantation

Serum lactic dehydrogenase (LDH) levels are mildly elevated in β-thalassemia major due to ineffective erythropoiesis. We reviewed the charts of 15 consecutive thalassemic children who underwent allogeneic, T-cell-depleted bone marrow transplantation (BMT) in our department during the last 3 years. Eleven patients had successful engraftment and are alive and well without evidence of disease, according to physical examinations, blood counts, and polymerase chain reaction (PCR) tests, with a median follow-up of 2 years. Two patients died due to transplantation-related complications, and two rejected the graft and received their backup autologous marrow. The LDH levels in the transplanted patients gradually decreased from an average of 952 ± 155 IU/L 10 days pre-transplant (N = 300–620) to 426 ± 56 IU/L at the day of transplantation, and stayed at approximately the same level post-transplant (489 ± 55 IU/L). By contrast, the LDH levels reverted to the pre-transplant value in those patients who rejected their marrow. The significance of this clinical observation for the pathophysiologic mechanism of intramedullary hemolysis and ineffective erythropoiesis in β-thalassemia major is discussed. © 1996 Wiley-Liss, Inc.