Summary:Telomere length indicates the replicative history of cells, serving as a molecular measure of the replicative potential remaining in cells. To investigate telomere length changes in hematopoietic stem cells, patients undergoing hematopoietic stem cell transplantation (HSCT) were evaluated. Fifteen patients after allogeneic bone marrow transplantation (allo-BMT group), seven patients after autologous peripheral blood stem cell transplantation (auto-PBSCT group), and 39 healthy controls were studied. Telomere length was measured in peripheral mononuclear cells by Southern blot hybridization. There was no significant difference between the allo-BMT and the auto-PBSCT groups. In the allo-BMT group, the mean telomere length of recipients was 2.01 kb shorter than that of their donors (P = 0.008), and was 1.59 kb shorter than that of agematched putative normal controls (P = 0.002). Telomere shortening in the allo-BMT group was equivalent to 41.4 years of aging in the donors, and to 52.4 years of aging in the normal controls. The mean telomere length in the auto-PBSCT group was 2.36 kb shorter than that of the age-matched putative controls (P = 0.043), which was equivalent to 61.5 years of aging in normal controls. The extent of telomere shortening in the allo-BMT group showed a trend to negative correlation with the number of mononuclear cells infused. These findings suggest that hematopoietic stem cells after HSCT lose telomere length and these shortened telomeres may result in a higher incidence of clonal disorders later in life.
Decreased lung function with exacerbation, and progressive decline of FEV(1) were observed in patients with TB-destroyed lung.
Osteoblast response to Ti implants depends not only on the chemistry of the implant but also on the physical properties of the implant surface, such as microtopography and roughness. This study was undertaken to examine early changes in cell morphology and gene expression during the early phase of osteoblast interaction with titanium alloy (Ti-6Al-4V) surfaces of two different roughnesses. MG63 osteoblast-like cells were cultured for 2, 6, 24, and 72 h on smooth (R a ϭ 0.18 Ϯ0.03 m) and rough (R a ϭ 2.95 Ϯ0.23 m) Ti-6Al-4V surfaces. Changes in cell proliferation were assessed by measuring cell number after 72 h in culture. Morphological characteristics were observed by scanning electron microscopy after 2, 6, and 24 h of culture. Changes in gene expression for extracellular signal-regulated kinase 2 (Erk2), type I collagen (␣ 2 [I] collagen), phospholipase C-␥2 (Plc-␥2), and -actin were measured by RT-PCR after 6 and 24 h in culture. Cell number was significantly higher on the smooth surface. In scanning electron micrographs, cells on smooth Ti-6Al-4V were spherical and raised up from the surface after 2 h in culture. In contrast, cells on the rough surface adopted an irregular, elongated shape that spanned across pits in the surface. At 24 h, cells on the smooth surface had flattened, become elongate, and covered the surface. In contrast, cells on the rough surface appeared more differentiated in shape and the margins of the cells were irregular, with many processes extending out, following the contour of the surface. Of the genes examined, only Erk2 and -actin showed a change in expression with surface roughness. Both genes were upregulated (p Ͻ 0.05) on the rough surface at 6 h. These results indicate that Ti-6Al-4V surface roughness affects osteoblast proliferation, morphology, and gene expression, and that these effects can be measured after periods as short as 2-6 h.
An extended medial to lateral approach for SFM during laparoscopic low anterior resection of rectal cancer appears to be an improvement over the previously used lateral approach, because it may provide a shorter operation time and shorter hospital stay.
Summary:Carboplatin hypersensitivity has rarely been reported in patients receiving repeated cycles of therapy, but has not been reported in transplant settings. We report a case of carboplatin hypersensitivity during conditioning for autologous PBSC transplantation. The patient suddenly developed chest tightness, hemoptysis, hypoxia and hypotension, resulting in a transient myocardial ischemia. The pathophysiologic mechanism for the event seemed to be non-immune-mediated direct histamine release given the lack of prior exposure to platinum. Contrary to advice not to continue further treatment with carboplatin by some authors, we successfully desensitized the patient and subsequently gave more carboplatin as a part of conditioning. Awareness of carboplatin as one of the causes of hypersensitivity may help avoid further problems either by substitution or desensitization, along with premedications. Keywords: carboplatin; hypersensitivity; conditioning; PBSC transplantation; desensitization Carboplatin, a second-generation, platinum-containing chemotherapeutic agent, is increasingly used in transplant conditioning regimens for a variety of solid tumors. Although type I hypersensitivity has been reported in 1% to 20% of patients who receive cisplatin, there are few reports of similar reactions in patients receiving repeated cycles of carboplatin therapy.1,2 To our knowledge, there have been no reported cases of life-threatening carboplatin hypersensitivity in the transplant setting.We report a case of carboplatin hypersensitivity who presented with hemoptysis and hypoxia resulting in transient myocardial ischemia during conditioning for autologous PBSC transplantation. Most of the patients reported who have had allergic reactions to carboplatin were unable to tolerate further treatment with it despite heavy premedication with steroids and antihistaminics. however, carboplatin was re-introduced successfully as a conditioning regimen after a course of desensitization. Case reportAn 8-year-old girl was admitted for autologous PBSC transplantation. One year earlier she had developed fever and jaundice, and was diagnosed to have a sarcoma botryoides arising in the bile duct. The tumor was stage III and only a partial resection was possible at that time. Chemotherapy consisting of vincristine, actinomycin-D and ifosfamide (VAI) along with radiotherapy had effected a good response on the second-look operation. A total of six leukaphereses were performed by CS3000+ after two mobilization cycles employing VAI plus G-CSF. The planned conditioning regimen was: carboplatin 800 mg/m 2 once daily i.v. on days Ϫ6 and Ϫ5, etoposide 200 mg/m 2 twice daily i.v. on days Ϫ6 to Ϫ4 (total six doses), and melphalan 180 mg/m 2 i.v. on day Ϫ2. The first morning dose of etoposide was administered uneventfully. Carboplatin was dissolved in 500 ml of D 5 . saline solution. Five minutes after starting the infusion when a total of about 10 mg of carboplatin had been administered, she suddenly developed tachypnea, chest tightness, cyanosis, vomit...
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