The experience of ligation of transverse or sigmoid sinus in surgery of large petroclival meningiomas

The authors present the experience of ligation of transverse or sigmoid sinus in the surgical removal of petroclival meningiomas. We reviewed the medical records and venograms of 14 patients with petroclival meningiomas, in whom the intraoperative ligation of transverse or sigmoid sinus had been done at our hospital between 1986 and 1999. All patients passed the intraoperative test clamping of the sinus. The drainage pattern of confluence of Herophili was classified into four types: type A, confluence and equal drainage on both transverse sinuses; type B, confluence and non-dominant transverse sinus on the tumor side; type C, confluence and dominant transverse sinus on the tumor side; and type D, unilateral transverse sinus only. Among the 14 cases, four cases were in type A, five cases in type B, and two were type C. There was no evidence of brain swelling after intraoperative test clamping of the sinus for more than 30 min. None of the patients experienced postoperative complications related with sinus ligation. Our observation suggests that the transverse or sigmoid sinus ligation is tolerable to patients who show the drainage patterns of type A, type B, and type C, if the test clamping proves to be safe.     

Orthotopic bone formation by implantation of apatite-coated poly(lactide-co-glycolide)/hydroxyapatite composite particulates and bone morphogenetic protein-2

Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. However, a delivery system is essential to take advantage of the osteoinductive effect of BMPs. In the present study, we tested the suitability of apatite-coated poly(D,L-lactide-co-glycolide)/nanohydroxyapatite (PLGA/HA) particulates as carriers for the controlled release of BMP-2. The release of BMP-2 from apatite-coated PLGA/HA particulates was sustained for at least 4 weeks in vitro. A delivery system of apatite-coated PLGA/HA particulates suspended in fibrin gel further slowed the BMP-2 release rate. In vivo implantation of either Fibrin gel + BMP-2 or Fibrin gel + apatite-coated PLGA/HA particulates showed enhanced new bone formation in critical-sized calvarial defects of rats 8 weeks after implantation, compared to implantation of fibrin gel only. Importantly, new bone formation was much higher in the defects treated with BMP-2 delivery using apatite-coated PLGA/HA particulates in fibrin gel (Fibrin gel + PLGA/HA + BMP-2 group) than in the defects treated either with apatite-coated PLGA/HA particulates in fibrin gel (Fibrin gel + BMP-2 group) or with BMP-2 delivery using fibrin gel alone (Fibrin gel + BMP-2 group). BMP-2 and osteoinductive HA had an additive effect on orthotopic bone formation. In conclusion, the apatite-coated PLGA/HA particulates showed good results as carriers for BMP-2. The BMP-2 delivery system showed high osteogenic capability in a rat calvarial bone defect model. The local and sustained delivery system for BMP-2 developed in this study may be useful as a carrier for BMP-2 and would enhance bone regeneration efficacy for the treatment of large bone defects.     

The comparison of esophageal variceal ligation plus propranolol versus propranolol alone for the primary prophylaxis of esophageal variceal bleeding

Background/Aims

To investigate the efficacy and longterm outcome of esophageal variceal ligation (EVL) plus propranolol in comparison with propranolol alone for the primary prophylaxis of esophageal variceal bleeding.

Methods

A total of 504 patients were retrospectively enrolled in this study. 330 patients were in propranolol group (Gr1) and 174 patients were in EVL plus propranolol group (Gr2). The endpoints of this study were esophageal variceal bleeding and mortality. Association analyses were performed to evaluate bleeding and mortality between Gr1 and Gr2.

Results

EVL was more applied in patients with high risk, such as large-sized varices (F2 or F3) or positive red color signs. Total 38 patients had bleeds, 32 in Gr1 and 6 in Gr2. The cumulative probability of bleeding at 120 months was 13% in Gr1 versus 4% in Gr2 (P=0.04). The predictive factors of variceal bleeding were red color signs (OR 2.962, P=0.007) and the method of propranolol plus EVL (OR 0.160, P=0.000). 20 patients died in Gr1 and 12 in Gr2. Mortality rates are similar in the two groups compared, 6.7% in Gr1 and 6.9% in Gr2. The cumulative probability of mortality at 120 months was not significantly different in the two groups (7% in Gr1, 12% in Gr2, P=0.798). The prognostic factors for mortality were age over 50 (OR 5.496, P=0.002), Child-Pugh class B (OR 3.979, P=0.001), and Child-Pugh class C (OR 10.861, P=0.000).

Conclusions

EVL plus propranolol is more effective than propranolol alone in the prevention of the first variceal bleeding in patients with liver cirrhosis.     

Effects of iontophoretically applied substance P, calcitonin gene-related peptide on excitability of dorsal horn neurones in rats

Spontaneous pain, allodynia and hyperalgesia are well known phenomena following peripheral nerve or tissue injury, and it is speculated that secondary hyperalgesia and allodynia, are generally thought to depend on a hyperexcitability (sensitization) of neurons in the dorsal horn. It is supposed that the sensitization may be due to various actions of neurotransmitters (SP, CGRP, excitatory amino acids) released from the primary afferent fibers. In this study, we examined effects of the iontophoretically applied SP and CGRP on the response to EAA receptor agonists (NMDA and non-NMDA) in the WDR dorsal horn neurones and see if the effects of SP or CGRP mimic the characteristic response pattern known in various pain models. The main results are summarized as follows: 1) SP specifically potentiated NMDA response. 2) CGRP non-specifically potentiated both NMDA and AMPA responses. Potentiation of NMDA response, however, was significantly greater than that of AMPA response. 3) 50% of SP applied cells and 15.8% of CGRP applied cells showed reciprocal changes(potentiation of NMDA response and suppression of AMPA response). These results are generally consistent with the sensitization characteristics in diverse pain models and suggests that the modulatory effects of SP and CGRP on NMDA and non-NMDA (AMPA) response are, at least in part, contribute to the development of sensitization in various pain models.     

The changes in coagulation profile and epidural catheter safety for living liver donors: a report on 6 years of our experience.

The use of epidural catheters has been a subject of active debate in living liver donors because of the possible postoperative coagulation derangement and the subsequent risk of epidural hematoma. The aim of this study was to evaluate the safety of epidural catheters in relation to the changes in coagulation profile based on a review of previously published literature and the results of our 360 donors. In both the literature and in our cases, platelet count, prothrombin time (PT), and activated partial thromboplastin time (aPTT) in cases of heparin administration showed significant changes (P < 0.05), especially after right lobectomy. Platelet count reached its nadir on postoperative day (POD) 2-3, while PT and aPTT reached their peaks on POD 1-2 and at the end of the operation, respectively. In our donors, the ranges of platelet count, PT, and aPTT for the first 3 PODs were 54-359 x10/microL, 0.99-2.38 international normalized ratio (INR), and 25.9-300 seconds, respectively, and of note, 5 donors (1.4%) had a platelet count of <80 x 10/microL and 9 donors (2.5%) had a PT of >2.0 INR. Epidural catheterizations were performed in 242 donors, and the catheters were removed on POD 3-4 in 177 donors (73.1%). Mean (range) of platelet count, PT, and aPTT on the day of catheter removal were 168.4 +/- 42.9 (82-307) x 10/microL, 1.33 +/- 0.18 (0.99-1.93) INR, and 40.9 +/- 4.8 (32.0-70.6) seconds, respectively. No epidural hematoma was observed in this study. In conclusion, the discreet use of epidural catheters in live liver donors, in spite of postoperative coagulation derangements, appears to be safe regardless of the type of hepatectomy performed.     

Sulfur and methane oxidation by a single microorganism

Natural and anthropogenic wetlands are major sources of the atmospheric greenhouse gas methane. Methane emissions from wetlands are mitigated by methanotrophic bacteria at the oxic–anoxic interface, a zone of intense redox cycling of carbon, sulfur, and nitrogen compounds. Here, we report on the isolation of an aerobic methanotrophic bacterium, ‘Methylovirgula thiovorans'' strain HY1, which possesses metabolic capabilities never before found in any methanotroph. Most notably, strain HY1 is the first bacterium shown to aerobically oxidize both methane and reduced sulfur compounds for growth. Genomic and proteomic analyses showed that soluble methane monooxygenase and XoxF-type alcohol dehydrogenases are responsible for methane and methanol oxidation, respectively. Various pathways for respiratory sulfur oxidation were present, including the Sox–rDsr pathway and the S₄I system. Strain HY1 employed the Calvin–Benson–Bassham cycle for CO₂ fixation during chemolithoautotrophic growth on reduced sulfur compounds. Proteomic and microrespirometry analyses showed that the metabolic pathways for methane and thiosulfate oxidation were induced in the presence of the respective substrates. Methane and thiosulfate could therefore be independently or simultaneously oxidized. The discovery of this versatile bacterium demonstrates that methanotrophy and thiotrophy are compatible in a single microorganism and underpins the intimate interactions of methane and sulfur cycles in oxic–anoxic interface environments.

Atmospheric methane (CH₄) is a potent greenhouse gas responsible for about 15% of the total greenhouse effect (1). The amount of CH₄ in Earth’s atmosphere is gradually increasing (2). The world’s largest single CH₄ source is natural wetlands, one-third of which are temperate and boreal northern wetlands (3, 4). Methane produced by the degradation of organic matter in anoxic sediments reaches the atmosphere via diffusion, transport through aerenchymous roots, or ebullition. Much of the diffusive flux of CH₄ is oxidized by aerobic methanotrophic bacteria at oxic–anoxic interfaces in wetlands, thereby limiting CH₄ emission (5–8). Methane formation is also prevented by the activity of microorganisms that redirect the flow of electrons and carbon away from methanogenic archaea, such as certain sulfur-cycling microorganisms. Microorganisms that respire sulfate (SO₄²⁻) or other oxidized sulfur compounds can contribute considerably to the anaerobic degradation of organic carbon in wetlands and outcompete methanogenic archaea (9, 10).Aerobic methanotrophic bacteria were long assumed to have a limited substrate spectrum, including methane, methanol, and occasionally other C1 compounds, but no other substrates (11). This assumption was overturned when it was discovered that methanotrophs of the genus Methylocella (family Beijerinckiaceae) use some simple organic acids, alcohols, and short-chain alkanes as alternative substrates to methane (11, 12). A few other alphaproteobacterial methanotrophs belonging to the Methylocystaceae or Beijerinckiaceae families, while not as versatile as Methylocella, have also been shown to metabolize acetate and/or ethanol (13–15). Two cultured Beijerinckiaceae methanotrophs even possess the genetic capacity for aerobic CO oxidation (16, 17), and the growth of one of them, ‘Methylocapsa gorgona'' MG08, was supported by CO in the presence of methane (18). In addition, thermophilic and mesophilic verrucomicrobial methanotrophs of the proposed genera ‘Methylacidiphilum'' and ‘Methylacidimicrobium'' grow autotrophically on CO₂ with H₂ as an electron donor (19–23). In fact, genes encoding NiFe hydrogenase are widespread in all major taxonomic families of methanotrophs, suggesting that H₂ may be a common supplemental energy source for these bacteria in nature. Recently, members of the genus Methylacidiphilum were also found to grow heterotrophically on various C3 compounds (24). Clearly, some methanotrophs can take advantage of other small-molecule substrates besides methane and methanol, which may enhance their survival and/or growth in natural habitats where CH₄ concentrations are low and/or variable (13).The oxidation of H₂ to two protons and the oxidation of CO to CO₂ both yield considerably lower standard free-energy changes, ΔG°′ = −237 kJ⋅mol⁻¹ H₂ and ΔG°′ = −249 kJ⋅mol⁻¹ CO, respectively, than the complete oxidation of CH₄ to CO₂ (ΔG°′ = −818 kJ⋅mol⁻¹ CH₄). In comparison, the standard free-energy changes for the oxidation of H₂S to SO₄²⁻ (ΔG°′ = −797 kJ⋅mol⁻¹ H₂S) and S₂O₃²⁻ to SO₄²⁻ (ΔG°′ = −818 kJ⋅mol⁻¹ S₂O₃²⁻) are similar to that for CH₄ oxidation. Based on these considerations, reduced sulfur compounds would be well-suited alternative substrates for methanotrophs.To date, there has been a clear distinction between thiotrophic and methanotrophic microorganisms. The growth of methanotrophs using reduced sulfur compounds as electron donors has never been reported. Recently, a member of the genus Methylacidiphilum was found to degrade methanethiol and sulfide for detoxification, but no growth benefit was observed from their oxidation (25). The common occurrence of sqr (encoding sulfide:quinone oxidoreductase) (Fig. 1) and mtoX (encoding methanethiol oxidase) (25) in methanotroph genomes suggests that detoxification mechanisms are common. However, genomes of some methanotrophs also harbor a complete Sox system (Dataset S1 and Fig. 1), and a recent study unveiled the co-occurrence of genes encoding sulfur (Sox and reverse dissimilatory sulfite reductase [rDsr]) and CH₄ (methane monooxygenase) oxidation systems in a metagenome-assembled genome recovered from a permafrost thaw wetland (26). These findings provide hints for a possible combination of thiotrophy and methanotrophy in particular bacteria. Here, we experimentally confirmed this hypothesis and isolated a facultative methanotroph (strain HY1) that harbors a complete repertoire of sulfur oxidation genes encoding the Sox–rDsr system (without soxCD).Open in a separate windowFig. 1.Phylogenomic tree and distribution of distinctive metabolic traits in methane- and sulfur-oxidizing bacteria in the classes Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, and Chlorobia. The tree includes 37 genomes and 2 metagenome-assembled genomes. Representative genomes of Sox-containing Alphaproteobacterial and Gammaproteobacterial methanotrophs were included. The tree was constructed based on 27 concatenated ribosomal proteins with FastTree implemented within Anvi’o phylogenomics workflow (details are in Materials and Methods). Black circles indicate 70% bootstrap support for nodes along the tree. A homology-based search for functional genes was performed by using BLAST (124), OrthoFinder (125), and manual examination (details are in Materials and Methods). Solid and open squares indicate the presence and absence of the genes, respectively.     

Relationship between Controlled Attenuation Parameter and Hepatic Steatosis as Assessed by Ultrasound in Alcoholic or Nonalcoholic Fatty Liver Disease

Background/Aims

The aim of this study was to evaluate the relationship between controlled attenuation parameter (CAP) and hepatic steatosis, as assessed by ultrasound (US) in patients with alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD).

Methods

Patients with either ALD or NAFLD who were diagnosed with fatty liver with US and whose CAP scores were measured, were retrospectively enrolled in this study. The degree of hepatic steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3).

Results

A total of 186 patients were included: 106 with NAFLD and 80 with ALD. Regarding hepatic steatosis, the CAP score was significantly correlated with US (ρ=0.580, p<0.001), and there was no significant difference between the NAFLD and ALD groups (ρ=0.569, p<0.001; ρ=0.519, p<0.001; p=0.635). Using CAP, area under receiver operating characteristic curves for ≥S2 and ≥S3 steatosis were excellent (0.789 and 0.843, respectively). For sensitivity ≥90%, CAP cutoffs for the detection of ≥S2 and ≥S3 steastosis were separated with a gap of approximately 35 dB/m in all patients and in each of the NAFLD and ALD groups.

Conclusions

The CAP score is well correlated with hepatic steatosis, as assessed by US, in both ALD and NAFLD.     

Tenofovir rescue therapy for chronic hepatitis B patients after multiple treatment failures

AIM: To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients after multiple failures.METHODS: A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue (NA) treatments were included. Study subjects were treated with TDF alone (n = 13) or in combination with lamivudine (LAM, n = 12) or entecavir (ETV, n = 4) for ≥ 6 mo. Complete virologic response (CVR) was defined as an achievement of serum hepatitis B virus (HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment. Safety assessment was based on serum creatinine and phosphorus level. Eleven patients had histories of LAM and adefovir dipivoxil (ADV) treatment and 18 patients were exposed to LAM, ADV, and ETV. Twenty-seven patients (93.1%) were hepatitis B e antigen (HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL. The median treatment duration was 16 mo (range 7 to 29 mo).RESULTS: All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it. Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV. One patient had a resistance to both ADV and ETV. The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%, respectively. Although one patient failed to achieve CVR, serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL, achieving near CVR. No patients in this study showed viral breakthrough or primary non-response during the follow-up period. The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%, 12%, and 27% at 6, 12, and 18 mo of treatment, respectively. Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations. History of prior exposure to specific antiviral agents did not make a difference to treatment outcome. Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV. No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed. There were no other adverse events related to TDF therapy observed in the study subjects.CONCLUSION: TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures.