Mammalian wound repair environment does not permit skeletal muscle regeneration

Repair and regeneration are mutually exclusive responses to injury. Previous studies have shown that wound fluids promote proliferation, but not differentiation, of myoblasts in vitro. This study explored the ability of the repair environment within polyvinyl alcohol sponges to support cellular events of skeletal muscle regeneration in vivo. Neonatal rat L8 myoblasts were modified to express beta-galactosidase then inoculated into plain sponges or sponges containing minced muscle. Labeled myoblasts were found in myotubes within minced muscle. In contrast, myoblasts inoculated into sponges lacking muscle remained mononucleate. Occurrence of labeled myoblasts within myotubes, which required fusion, represents differentiation of inoculated myoblasts to participate in regeneration. Failure of myoblasts to form myotubes in sponges lacking muscle suggests that this wound repair environment cannot support morphologic differentiation of myoblasts. Although this repair environment can support the survival of myoblasts, it did not support myogenesis, an event necessary to complete skeletal muscle regeneration. Data from this study reinforce earlier studies in vitro and suggest that the properties attributed to wound fluids are inherent in the wound environment. Whether the inability of this environment to support myogenesis is the consequence of the absence of essential factors or the presence of inhibitors remains to be determined.     

Liver transplantation for chronic hepatitis B with lamivudine-resistant YMDD mutant using add-on adefovir dipivoxil plus lamivudine.

Lamivudine treatment in patients with chronic hepatitis B virus (HBV) infection may improve clinical state and suppress viral replication before liver transplantation. Emergence of lamivudine-resistant YMDD mutant is common. We report the results of liver transplantation in 16 patients with pretransplantation YMDD mutants after receiving lamivudine treatment for a median of 738 days (range, 400-1799 days). Adefovir dipivoxil (10 mg daily) was added on to lamivudine for a median of 20 days (range, 8-271 days) before (n = 11) or at (n = 5) liver transplantation, and the combination was continued indefinitely thereafter. Eight patients received additional intravenous hepatitis B immune globulin (HBIG) for a median of 24 months. Fifteen patients with known pre-adefovir HBV DNA levels had a median titer of 14,200 x 10(3) copies/mL (2 x 10(3) to 4,690,000 x 10(3) copies/mL), and 14 had HBV DNA >10(5) copies/mL. All but 1 patient remained positive for HBV DNA (by quantitative polymerase chain reaction [qPCR]) at the time of liver transplantation, and the titer was greater than10(5) copies/mL in 8 patients. The median follow-up after liver transplantation was 21.1 (range, 4.4-68.9) months. One patient (6%) died of an unrelated cause 12.2 months after transplantation, and 15 patients (94%) were alive with the original graft. All patients cleared HBV DNA and had no detectable HBV DNA by qPCR at the latest follow-up. Fourteen patients had cleared hepatitis B surface antigen (HBsAg), but 2 patients who received only adefovir dipivoxil and lamivudine without HBIG remained HBsAg positive after 7.7 and 9.5 months. Serum HBV DNA, however, was negative, and there was no biochemical or histological evidence of recurrence. Adefovir dipivoxil was well tolerated with no significant renal toxicity. In conclusion, a combination of add-on adefovir dipivoxil plus lamivudine therapy provides effective prophylaxis in patients with pretransplantation YMDD mutant that may be actively replicating. The cost effectiveness of additional passive immunoprophylaxis remains to be defined.     

Effect of photodynamic therapy on blood flow in normal and tumor vessels

The aim of this series of experiments was to determine the dynamic blood flow changes that occur in normal and neoplastic tissues during photodynamic therapy. Mice bearing SMT-F tumors and rats with transplanted chondrosarcomas were injected with graded doses of dihematoporphyrin ether. Studies of changes in single-vessel and whole-tumor blood flow were carried out with 630 nm light activation. A helium neon laser Doppler velocimeter was used to stimulate dihematoporphyrin ether, as well as to measure changes in flow velocity in both single-vessel and whole-tumor models. There was a reduction of flow velocity in all vessels and tumors in animals injected with 1 to 40 mg/kg dihematoporphyrin ether intraperitoneally. The extent of flow reduction was related to drug dose administered. Decreases in blood flow began within 10 seconds of light stimulation and were maximal within 5 minutes. Both normal and tumor vessels responded similarly. We conclude that photodynamic therapy leads to significant microcirculatory changes that may be pertinent to the mechanism of tumor necrosis.     

Congenital absence of the inferior rectus muscle--diagnosis and management.

BACKGROUND: Congenital absence of the inferior rectus muscle is a rare cause of apparent inferior rectus palsy especially in the absence of associated cranial facial anomalies. METHODS: We report three cases of isolated congenital absence of the inferior rectus muscle and its successful surgical management. RESULTS: Failure of the normal embryologic development of the mesodermal complex around the eye can lead to agenesis of the extraocular muscles. In apparent palsies of the inferior rectus muscle and no definite cause, a high index of suspicion and orbital imaging can confirm the diagnosis of congenitally absent inferior rectus preoperatively. Surgical correction may involve inferior transposition of the horizontal rectus muscles. CONCLUSIONS: Although rare, congenital absence of the inferior rectus muscle is a possible cause of apparent inferior rectus muscle palsy particularly in the absence of another identifiable cause. Strabismus surgery in conjunction with intramuscular botulinum toxin injection can offer significant improvement in function and cosmesis of these patients.     

Intracranial metastasis from clear cell sarcoma of the kidney--a case report.

Childhood kidney tumors seldom metastasize into the cranial cavity unless it is a special histological variant. We report a 4-year-old boy with multiple intracranial metastases in the left parietotemporal and right cerebellar area from primary clear cell sarcoma of the kidney without evidence of bony metastases. Metastatic tumor revealed nests of uniformly polygonal cells with clear cytoplasm demarcated by delicate fibrovascular arcades. Tumor cells were positive for vimentin and negative for cytokeratin, S-100 protein, desmin, and myoglobin. Cellular proliferation rate measured by PCNA, and Ki-67 was not significantly different between primary tumor mass and metastatic brain lesion. Expression of p53 oncoprotein was not evident in both lesions. These findings suggested that the relapse and metastasis of clear cell sarcoma of the kidney was probably due to regrowth of micro-metastases which were present at an early stage of disease.     

高脂血症患者C—反应蛋白含量的变化及氟伐他汀对它的影响

OBJECTIVE: To observe the changes of C-reactive protein (CRP) level and its relationship with blood lipids, and the effects of fluvastatin on CRP and the lipids in patients with hyperlipidemia. METHODS: Serum levels of cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C) and lipoprotein(a)[Lp(a)] were measured by enzyme assay, and plasma CRP level by immunonephelometry before and after fluvastatin treatment (20 mg/d for 4 weeks) in patients with hyperlipidemia. RESULTS: CRP levels were above normal in 90.3% hyperlipidemia cases in spite of the various accompanying diseases. Fluvastatin treatment significantly reduced TC (-7.49%), TG (-14.32%), LDL (-13.88%), VLDL (-18.48%) and TC/HDL(-13.50%) levels (P<0.01), and also brought down Lp(a) concentration (-13.81%). CRP levels was very effectively reduced after the treatment (-15.92%, P<0.001). No association between basal CRP levels and basal lipids and Lp(a) concentrations was observed. Positive correlation of CRP, however, was observed after fluvastatin treatment with TC/HDL (r=0.62, P=0.041) and Lp(a) (r=0.320, P=0.011), while inverse relations were noted between CRP and HDL (r=-0.288, P=0.023). CONCLUSION: CRP levels increases markedly in patients with hyperlipidemia, a fact that is independent of the accompanying diseases. In addition to modulating blood lipid levels, fluvastatin also reduces CRP level, the latter possibly serving as an independent predictive factor for atherosclerotic cardiovascular diseases and also as an indicator for estimating the effectiveness of the treatment.     

Chronic hepatitis B virus infection in patients with “Normal” ALT levels

Not many data exist to guide us in the management of patients with chronic hepatitis B virus infection and “normal” alanine aminotransferase levels. Many of these patients may not have normal levels on long-term follow-up or when the upper limit of normal is determined from a truly healthy reference population. These patients may have significant histologic disease and benefit from further investigation or treatment. This article focuses on the disease course of such patients.