Preparation of ABCBA-type block copolymers by use of macro-initiators containing peroxy and azo groups

Some new macroinitiators ( 5 ) containing azo and peroxy groups were synthesized by transformation of esters of poly(ethylene glycol) ( 1 ) (PEG) of different molecular weight with hydroxyl end groups and an azo group in the middle into the corresponding polymers with tert-butylperoxycarbonyl end groups by reaction with terephthaloyl chloride and subsequently with tert-butyl hydroporoxide. Decomposition in the presence of styrene at 60°C or with 3,6,9-triazaun-decane-1,11-diamine in presence of methyl methacrylate gave the corresponding ABA block copolymer 6 and the ABBA block copolymer 7 , respectively. Both block copolymers were used as polymeric initiators. The ABCBA block copolymer 8 was synthesized from 6 and methyl methacrylate or from 7 and styrene by thermally induced polymerization at 80°C. The resulting block copolymers were separated from the homopolymers by selective solvent extraction and characterized by spectroscopic and fractional precipitation methods.     

Bone marrow transplantation from matched siblings in patients with fanconi anemia utilizing low-dose cyclophosphamide, thoracoabdominal radiation and antithymocyte globulin

Nineteen patients with Fanconi anemia (FA) and bone marrow failure underwent bone marrow transplantation (BMT) from matched siblings. Median age at BMT was 8.7 years. Conditioning consisted of low-dose cyclophosphamide (CY 5 mg/kg x 4 days) and thoracoabdominal irradiation (TAI 400 cGy). Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A (CsA) in 13 patients and CsA plus methotrexate in 6 patients. Antithymocyte globulin (ATG) was added in the pretransplant as well as the post-transplant period. All patients received high-dose acyclovir from day 2 pre-BMT to day 28 post BMT, and intravenous immunoglobulins (IVIG), 500 mg/kg weekly from day 7 pre-BMT to day 90 post BMT. No fungal prophylaxis was given. All patients engrafted, (median, 14 days for an absolute neutrophil count > or =0.5 x 10(9)/l; median, 37 days for platelet count > or =20 x 10(9)/l). Fourteen (74%) patients are alive with sustained engraftment and are transfusion independent. Three (16.6%) patients developed acute GVHD; none developed chronic GVHD. Five (26%) patients developed invasive fungal infections, and two (10%) developed fatal CMV disease. We believe the addition of ATG may have contributed to the increased incidence of severe life-threatening fungal and viral infections in our series.     

Effects of 10?days of modest intermittent hypoxia on circulating measures of inflammation in healthy humans

Purpose

Obstructive sleep apnea (OSA) is a common disease which is associated with elevated inflammatory markers and adhesion molecules, possibly due to nightly intermittent hypoxia (IH). The purpose of this study was to test the hypothesis that IH would increase systemic inflammatory markers in healthy human males.

Methods

Healthy, young male subjects (n?=?9; 24?±?2?years) were exposed to a single daily isocapnic hypoxia exposure (oxyhemoglobin saturation?=?80%, 1?h/day) for 10 consecutive days. Serum granulocyte macrophage colony-stimulating factor, interferon-??, interleukin-1??, interleukin-6, interleukin-8, leptin, monocyte chemotactic protein-1, vascular endothelial growth factor, intracellular adhesion molecule-1, and vascular cell adhesion molecule-1 were measured before and following the 10?days of IH using Luminex.

Results

Nine subjects completed the study (24?±?2?years; 24?±?2?kg/m²). The mean oxyhemoglobin saturation was 80.8?±?1.6% during the hypoxia exposures. There was no significant change in any of the markers of inflammation (paired t test, P?>?0.2 all cytokines).

Conclusions

These findings suggest that (1) a more substantial or a different pattern of hypoxemia might be necessary to activate systemic inflammation, (2) the system may need to be primed before hypoxic exposure, or (3) increases in inflammatory markers in patients with OSA may be more related to other factors such as obesity or nocturnal arousal.     

Levels of gingival tissue platelet activating factor after conventional and regenerative periodontal surgery

The hypothesis, a relationship between gingival tissue platelet activating factor (PAF) levels and healing after periodontal surgery, was tested by measuring PAF levels in gingival tissues collected from sites that had undergone flap surgery and guided tissue regeneration (GTR) or flap surgery alone. Using a split-mouth design, 20 intrabony defects were randomly assigned to treatment with flap surgery and GTR (group 1) or with flap surgery alone (group 2). Gingival tissue samples were obtained at surgery (baseline) and at 6-month follow-up evaluation visit. One half of each sample was used for analysis of PAF levels by high-performance liquid chromatography, and the other half of the sample was used for histomorphometric analysis that included measurements of number and diameter of blood vessels. PAF levels and diameter of blood vessels were significantly decreased (p < 0.01), and the number of blood vessels was significantly increased (p < 0.05) in both groups after 6 months compared to the baseline values. Postoperative number of blood vessels were significantly higher in group 1 (p < 0.05), whereas there was no significant difference in postoperative PAF levels between the two groups (p > 0.05). Based on the reported results, it is suggested that a decrease in gingival PAF levels might be found after conventional and regenerative periodontal surgery.     

Comparison of the proliferative activity in gingival epithelium after surgical treatments of intrabony defects with bioactive glass and bioabsorbable membrane

Guided tissue regeneration is based on preventing the more rapidly proliferating epithelium from growing into the periodontal defect after surgical procedures incorporating barrier membranes. The aim of this study was to compare the proliferative activity of gingival epithelium using proliferating cell nuclear antigen (PCNA) as a marker of cell proliferation after surgical treatments with bioactive glass graft material and bioabsorbable membrane. Using split mouth design, 20 intrabony defects were randomly assigned treatments with bioactive glass (BG group) or bioabsorbable membrane (BM group). Gingival biopsies were taken at preoperative and postoperative 12 weeks. After histological processing, the number of the inflammatory cells was measured in hematoxylin and eosin-stained sections; PCNA expression was determined in immunohistochemically-stained sections. At postoperative 12 weeks, the number of the inflammatory cells was significantly decreased (p < 0.01), PCNA expression was significantly increased (p < 0.001) in both treatment groups compared to baseline data. There was no significant difference in PCNA expression between baseline values of two groups (p > 0.05), while at postoperative 12 weeks, increase in BG group was significantly greater than that in BM group (p < 0.001). These results suggest that epithelial cell proliferation is more prominent after treatment of intrabony defects with bioactive glass compared to the treatment with bioabsorbable membrane.     

Stem cell transplantation for patients with Fanconi anemia with low-dose cyclophosphamide and antithymocyte globulins without the use of radiation therapy

In all, 22 patients with confirmed Fanconi anemia (FA) underwent stem cell transplantation (SCT) from HLA-matched, related donors at KFSHRC. Median age at SCT was 7.6 years (range, 2.5-14.6 years). Conditioning regimen consisted of cyclophosphamide (CY) 15 mg/kg/day intravenously (i.v.) for 4 consecutive days, in addition to equine antithymocyte globulins (ATG) given i.v. at 40 mg/kg/day for four doses pre-SCT. No radiation therapy was given. For graft-versus-host disease prophylaxis, we used cyclosporin at the standard doses; ATG was added at 20 mg/kg/dose i.v. on days 2, 4, 6, 8, 10, and 12 post-SCT (total of six doses). All patients engrafted and are alive and transfusion independent with a median follow-up time of 20.2 months (range, 3.3-59 months). One patient however developed a decrease in her WBC and platelet count. Her work-up revealed slightly hypocellular bone marrow, and a series of chimerism studies over 1 year confirmed that she has stable mixed chimerism; she remains transfusion independent. We conclude that low-dose CY without radiation therapy can be used satisfactorily in the conditioning of patients with FA undergoing related SCT.     

A case of endodermal sinus tumor associated with the first pregnancy and successful management of the second pregnancy: a case report and review of the literature

BACKGROUND: Pregnancy complicated by endodermal sinus tumor (EST) of the ovary has rarely been reported. CASE: A huge ovarian EST causing bowel obstruction was found in a 22-year-old patient at 34 weeks of gestation. Abnormally high alpha-fetoprotein (AFP) levels suggested a malignant germ cell tumor of the ovary. The patient was submitted to cesarean section and fertility sparing surgery, and then received four courses of combination chemotherapy. There was no evidence of recurrence 19 months after initial treatment but transvaginal ultrasound (US) evaluation showed an intrauterine pregnancy of six weeks. We delivered a 3,200 g healthy male baby with Apgar scores of 8 and 9 by elective cesarean section at 39 weeks of gestation. CONCLUSIONS: Successful outcome of a second pregnancy is possible after treatment with fertility sparing surgery and combination chemotherapy for an endodermal sinus tumor associated with a first pregnancy. Moreover checking of weekly AFP levels and performing monthly abdominal US could be effective for surveillance of these pregnancies. However management of EST during pregnancy should be based on consideration of the patient's presenting condition, preferences, and gestational age.     

Successful medical treatment of cesarean scar pregnancy: a case report

OBJECTIVE: Cesarean scar pregnancy is implantation of the pregnancy within the fibrous tissue of the cesarean scar which is completely surrounded by myometrium. METHOD AND RESULT: A 32-year-old woman, gravida 2, para 1 presented at our emergency department with mild lower abdominal pain and minimal vaginal bleeding. She was diagnosed with cesarean scar pregnancy. Conservative treatment with methotrexate 50 mg/m2 was administered IM on days 0 and 8. Her betaHCG value was zero at the 14th week after beginning of the treatment. CONCLUSION: Repeated methotrexate administration in the management of cesarean scar pregnancy should be attempted in informed patients who especially desire fertility and can be closely followed up.     

Influence of Age on Acute and Chronic GVHD in Children Undergoing HLA-Identical Sibling Bone Marrow Transplantation for Acute Leukemia: Implications for Prophylaxis

Relapse remains the major cause of mortality after hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research has suggested that reducing the intensity of calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis may be an effective strategy for abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that the benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD. We conducted a study of risk factors for GVHD, to risk-stratify patients based on age. Patients age <18 years with leukemia who received myeloablative, T cell-replete MSD bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis between 2000 and 2013 and were entered into the Center for International Blood and Marrow Transplant Research registry were included. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 19%, that of grade II-IV aGVHD 7%, and that of chronic GVHD (cGVHD) was 16%. Compared with age 13 to 18 years, age 2 to 12 years was associated with a lower risk of grade II-IV aGVHD (hazard ratio [HR], .42; 95% confidence interval [CI], .26 to .70; P?=?.0008), grade II-IV aGVHD (HR, .24; 95% CI, .10 to .56; P?=?.001), and cGVHD (HR, .32; 95% CI, .19 to .54; P?<?.001). Compared with 2000-2004, the risk of grade II-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .36; 95% CI, .20 to .65; P?=?.0007) and in 2009-2013 (HR, .24; 95% CI. .11 to .53; P?=?.0004). Similarly, the risk of grade III-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .23; 95% CI, .08 to .65; P?=?.0056) and 2009-2013 (HR, .16; 95% CI, .04 to .67; P?=?.0126) compared with those doing so in 2000-2004. We conclude that aGVHD rates have decreased significantly over time, and that children age 2 to 12 years are at very low risk for aGVHD and cGVHD. These results should be validated in an independent analysis, because these patients with high-risk malignancies may be good candidates for trials of reduced GVHD prophylaxis.