Microvascular response in the periosteum following mucoperiosteal flap surgery in dogs: angiogenesis and bone resorption and formation

BACKGROUND: When surgical stress reaches the periosteum, bone resorption and formation that occur as a periosteal response are closely related to angiogenesis and hemodynamics. Thus, we investigated bone remodeling in the healing process after mucoperiosteal flap surgery, focusing our attention on the microcirculation. METHODS: Mucoperiosteal flap surgery was performed on 12 adult beagle dogs. The periosteal vascular plexus was observed on days 7, 14, 21, and 28 after surgery, using three different techniques: in histological specimens into which India ink was injected into blood vessels, under a light microscope; in ultrathin sections, using a transmission electron microscope; and in acryl plastic-injected vascular corrosion cast specimens, under a scanning electron microscope. RESULTS: On day 7 after surgery, the interstitum of the elevated mucoperiosteal vascular plexus was filled with sinusoidal new blood vessels. Bone resorption by osteoclasts was observed around these new blood vessels and many highly permeable fenestrations were present in the vascular endothelium. On day 14 after surgery, sinusoidal new blood vessels were more markedly developed and some regions exhibited glomeruluslike morphology consistent with bone resorption cavities. Activated osteoblasts were present around these new blood vessels and highly permeable vesicles, which were considered to be possible vesiclo-vacuolar organelles (VVOs) and caveolae, were noted in the vascular endothelium. On days 21 and 28 after surgery, the mucoperiosteal vascular plexus was dissected through regression of endothelial cells and fibroblasts and reconstructed into a rough mesh structure, and simultaneously the bone surface became smooth. CONCLUSION: The morphology of the mucoperiosteal vascular plexus changed with bone metabolism and these changes contributed to transport of substances involved in periodontal repair.     

Randomized controlled study of gemcitabine plus S-1 combination chemotherapy versus gemcitabine for unresectable pancreatic cancer

Purpose

The aim of this study was to evaluate efficacy and safety of gemcitabine plus S-1 (GS) combination chemotherapy in patients with unresectable pancreatic cancer.

Methods

Patients were randomly assigned to receive GS (oral S-1 60 mg/m² daily on days 1–15 every 3 weeks and gemcitabine 1,000 mg/m² on days 8 and 15) or gemcitabine (1,000 mg/m² on days 1, 8, and 15 every 4 weeks). The primary endpoint was progression-free survival (PFS).

Results

One hundred and one patients were randomly assigned. PFS was significantly longer in the GS arm with an estimated hazard ratio (HR) of 0.65 (95 % CI 0.43–0.98; P = 0.039; median 5.3 vs 3.8 months). Objective response rate (ORR) was also better in the GS arm (21.6 vs 6 %, P = 0.048). Median survival was 8.6 months for GS and 8.6 months for GEM (HR 0.93; 95 % CI 0.61–1.41; P = 0.714). Grade 3–4 neutropenia (44 vs 19.6 %, P = 0.011) and thrombocytopenia (26 vs 8.7 %, P = 0.051) were more frequent in the GS arm.

Conclusions

GS therapy improved PFS and ORR with acceptable toxicity profile in patients with unresectable pancreatic cancer.     

Comparisons of femoral tunnel enlargement in 169 patients between single-bundle and anatomic double-bundle anterior cruciate ligament reconstructions with hamstring tendon grafts

Purpose  

Authors have hypothesized that the incidence and the degree of femoral tunnel enlargement after the hamstring ACL reconstruction may be significantly less in the anatomic double-bundle procedure than in single-bundle procedure. The purpose of this study is to test this hypothesis.     

Quantitative histological study of the sural nerve in a child with acid maltase deficiency (glycogenosis type II)

A boy diagnosed as having glycogenosis type II at three years of age, underwent a sural nerve biopsy at the age of seven years. The distribution of the diameters of myelinated nerve fibers did not clearly demonstrate a bimodal pattern. However, larger fibers of 8 μm or more in diameter were more abundant. This finding correlated with the motor conduction velocity which was within normal limits for his age. A striking feature was the accumulation of glycogen particles in Schwann cells of both myelinated and unmyelinated nerve fibers. The accumulation of glycogen particles was more prominent in Schwann cells of myelinated nerve fibers than in those of unmyelinated ones. The reason for this finding is unclear. The accumulation of glycogen particles in nerve fibers was less than that found in muscle fibers. These morphologic differences between muscle and peripheral nerve fibers may represent an intrinsic difference between the two tissues; glycogen turnover may be faster in muscle than in nerve cells.     

Nitric oxide acts on the mitochondria and protects human endothelial cells from apoptosis

Proliferation of small blood vessels in synovial tissues is one of the pathologic features of rheumatoid arthritis. In this study we tested the hypothesis that nitric oxide (NO) protects endothelial cells (ECs) against apoptogenic agents in vitro. Human umbilical-vein endothelial cells (HUVECs) were cultured with and without NO donor S -nitro- N -acetylpenicillamine (SNAP) and further incubated in the presence or absence of Z-leucine-leucine-leucine-aldehyde (LLL-CHO), etoposide, or C2-ceramide. After cultivation, apoptosis of HUVECs was quantified on the basis of disruption of mitochondrial transmembrane potential (DeltaPsim), activation of caspases, and the presence of hypodiploid DNA-positive cells. Treatment of HUVECs with LLL-CHO, etoposide, or C2-ceramide induced DeltaPsim, activation of caspase-3, caspase-8, and caspase-9 and the appearance of hypodiploid DNA-positive cells. NO production in HUVECs was clearly increased by SNAP. Apoptotic cell death in HUVECs induced by LLL-CHO, etoposide, and C2-ceramide was significantly suppressed by SNAP treatment. HUVECs in vitro expressed Bcl-2, Bcl-xL, and Bax; however, expression was not changed by SNAP treatment in the presence or absence of LLL-CHO, etoposide, or C2-ceramide. Although the molecule(s) responsible for the protective effects of NO remains to be identified, our data imply that NO protects HUVECs against mitochondrial perturbation caused by apoptogenic agents. These results suggest that NO promotes endothelial-cell proliferation and angiogenesis in the synovial tissues of patients with rheumatoid arthritis and that NO may be a therapeutic target for rheumatoid arthritis.     

Clinical outcome and survival of secondary (AA) amyloidosis

OBJECTIVE: In order to predict the clinical outcome of secondary (AA) amyloidosis patients with rheumatic diseases, we studied the clinical features at presentation of AA amyloidosis. METHODS: We investigated the clinical characteristics and survival of 42 patients with biopsy-proven AA amyloidosis who were followed up in our department from 1983 to 2001. RESULTS: A presenting factor which adversely influenced clinical outcome was a raised serum creatinine concentration at the time AA amyloidosis was diagnosed. Eight of 42 patients survived for 10 years or more after the presentation of AA amyloidosis, while 24 patients had died within 10 years. At the diagnosis of AA amyloidosis, cardiac involvement was detected in 11 of 24 non-survivors, whereas it was not detected in any of the 8 long-term survivors. Estimated survival at 5 years was 31.3% in those who had cardiac involvement, and was 63.3% in those who had no cardiac involvement at the presentation of AA amyloidosis. CONCLUSION: Our results indicate that clinical outcome is related to renal function and cardiac involvement at the time AA amyloidosis is diagnosed. Amyloid-related cardiac involvement is one of the unfavorable predictive factors in AA amyloidosis patients.     

Successful combined therapy of cyclophosphamide and cyclosporine for acute exacerbated interstitial pneumonia associated with dermatomyositis

Interstitial pneumonia of polymyositis and dermatomyositis (PM/DM), especially the rapid progressive type, is a serious complication. We report a case of acute exacerbated interstitial pneumonia associated with DM. The respiratory distress condition was refractory to steroid pulse therapy and cyclosporine, however, there was a good response to additional intravenous cyclophosphamide pulse therapy (IVCY). We propose the possibility that the combination of these immunosuppressants might be useful for interstitial pneumonia with DM which is resistant to conventional steroid therapies.     

Successful treatment of chronic lupus myocarditis with prednisolone and mizoribine

A 36-year-old female patient who was diagnosed with chronic myocarditis as an initial manifestation of systemic lupus erythematosus (SLE) was admitted to our hospital. At her third occurrence of heart failure, we performed an endomyocardial biopsy and proved chronic myocarditis with SLE. Subsequently, she was treated with prednisolone and the immunosuppressive agent mizoribine (MZR), and her cardiac function improved. We describe for the first time treatment with MZR for chronic cardiac involvement of SLE.