Total Intravenous Anesthesia with Propofol Reduces Postoperative Nausea and Vomiting in Patients Undergoing Robot-Assisted Laparoscopic Radical Prostatectomy: A Prospective Randomized Trial

Purpose

We investigated the effect of total intravenous anesthesia (TIVA) with propofol on postoperative nausea and vomiting (PONV) after robot-assisted laparoscopic radical prostatectomy (RLRP) in patients at low risk of developing PONV, in comparison to balanced anesthesia with desflurane.

Materials and Methods

Sixty two patients were randomly assigned to the Des or TIVA group. Propofol and remifentanil were used for induction of anesthesia in both groups and for maintenance of the anesthesia in the TIVA group. In the Des group, anesthesia was maintained with desflurane and remifentanil. In both groups, postoperative pain was controlled using fentanyl-based intravenous patient controlled analgesia, and ramosetron 0.3 mg was administered at the end of surgery. The incidence of PONV, severity of nausea and pain, and requirements of rescue antiemetics and analgesics were recorded.

Results

The incidence of nausea in the post-anesthetic care unit was 22.6% in the Des group and 6.5% in the TIVA (p=0.001) group. The incidence of nausea at postoperative 1-6 hours was 54.8% in the Des group and 16.1% in the TIVA group (p=0.001). At postoperative 6-48 hours, there were no significant differences in the incidence of nausea between groups.

Conclusion

In order to prevent PONV after RLRP in the early postoperative period, anesthesia using TIVA with propofol is required regardless of patient-related risk factors.     

Clinical Features and the Diagnostic Value of Component Allergen-Specific IgE in Hymenoptera Venom Allergy

Purpose

Although patient history is vital for the diagnosis of hymenoptera venom allergy, specific IgE detection is also important to identify the culprit insect and monitor the effect of immunotherapy. We evaluated the diagnostic value of serum-specific IgE detection of hymenoptera venom component allergens and documented changes in allergen-specific IgE after immunotherapy.

Methods

Fifty-six hymenoptera venom allergy patients receiving venom immunotherapy were recruited from Ajou University Hospital, Korea. The clinical manifestations of the patients were noted, and serum-specific IgE detection was performed, using conventional venom extracts as well as component allergens. Data were analyzed retrospectively.

Results

A total of 35 (62.5%) patients were male, and 33 (73.3%) patients were atopic. The mean patient age was 44.9±13.8 years. Localized reactions occurred in 23.2% of patients, and systemic reactions occurred in 76.8%. The most common clinical manifestations included skin involvement, such as urticaria and angioedema, and respiratory involvement. Yellow jackets were the most frequent culprit insect, followed by yellow hornets, white-faced hornets, honeybees, and paper wasps, as determined at the time of diagnosis. Double sensitization to both Apidae and Vespidae species was detected in 70.9% of patients. The positive predictive values (PPV) of rVes v 5-specific and rPol d 5-specific IgE detection were 85.7% and 87.5%, respectively, which correlated well with conventional venom extract-specific IgE detection (r=0.762 and r=0.757, respectively). In contrast, the PPV of rApi m 1-specific IgE detection at the time of diagnosis was 34.8%. Three years of venom immunotherapy resulted in decreased venom-specific IgE, particularly IgE specific for Vespidae venom components.

Conclusions

Stings by yellow jackets and male sex may be risk factors for hymenoptera venom allergy in Korea. Vespidae component-specific IgE, but not Apidae component-specific IgE, had diagnostic and monitoring value in hymenoptera venom allergy comparable to that of conventional hymenoptera venom extract-specific IgE.     

Soluble tumor necrosis factor receptor: enbrel (etanercept) for subacute pulmonary dysfunction following allogeneic stem cell transplantation

Subacute lung disease, manifested as either obstructive (OLD) or restrictive (RLD) lung dysfunction, is a common complication following allogeneic stem cell transplantation. In each case, therapeutic options are limited, morbidity remains high, and long-term survival is poor. Between 2001 and 2008, 34 patients with noninfectious, obstructive (25) or RLD restrictive lung dysfunction (nine) received etanercept (Enbrel?, Amgen Inc.) 0.4 mg/kg/dose, subcutaneously, twice weekly, for 4 (group A) or 12 weeks (group B). Corticosteroids (if present at study entry) were kept constant for the initial 4 weeks of therapy and then tapered as tolerated. Thirty-one of 34 (91%) subjects were evaluable for response, and 10 (32%) met primary response criteria. There was no difference in response based on the duration of treatment (29% group A versus 35% group B; P = .99), the presence of RLD or OLD (33% versus 32%; P = .73), or the severity of pulmonary disease at study onset. Estimated 5-year overall survival rates following therapy were 61% (95% confidence interval, 46%-80%) for all subjects and 90% (95% confidence level, 73%-100%) for the 10 who met the primary response criteria. Five-year survival estimates for subjects treated with RLD was 44%, compared with 67% for those treated for OLD (P = .19). Etanercept was well tolerated, with no bacteremia or viremia observed. Pathogens were noted on posttherapy bronchoalveolar lavage in two cases. These data support the development of expanded clinical trials to study etanercept as a therapeutic agent for subacute lung injury after allogeneic stem cell transplantation.     

Prevalence of the CTNNB1 mutation genotype in surgically resected fibromatosis of the breast

Kim T, Jung E A, Song J Y, Roh J H, Choi J S, Kwon J E, Kang S Y, Cho E Y, Shin J H, Nam S‐J, Yang J H & Choi Y‐L
(2012) Histopathology  60, 347–356
Prevalence of the CTNNB1 mutation genotype in surgically resected fibromatosis of the breast Aims: To investigate CTNNB1 mutation and β‐catenin expression in resected breast fibromatosis and to identify potential molecular markers of fibromatosis of the breast. Methods and results: We selected 12 patients with fibromatosis of the breast who underwent surgical resection and were confirmed by histological examination. Ultrasonography findings for 10 patients were reviewed and only two cases were suspicious for fibromatosis on imaging. On core needle biopsy for pre‐operative diagnoses, only three cases were histologically suspicious for fibromatosis. Mutations in exon 3 of CTNNB1 were detected by direct DNA sequencing in nine (75.0%) cases: all were c.121G>A (p.T41A), which was much more frequent in breast fibromatoses than in other soft tissue lesions. Nuclear β‐catenin expression was observed in all cases and the level of expression was higher in cases with mutation. In eight of nine cases, the matched biopsy specimen showed the same CTNNB1 mutation status as the pre‐operative specimen. Conclusions: In the majority of cases, clinical presentation and breast imaging are highly suspicious for carcinoma. Definitive pre‐operative pathological diagnosis by core needle biopsy is difficult. CTNNB1 mutation and nuclear β‐catenin expression are frequently detected in sporadic breast fibromatoses, suggesting their potential as a useful tool to distinguish breast fibromatoses from other neoplasms.     

TNF-Inhibition with Etanercept for Graft-versus-Host Disease Prevention in High-Risk HCT: Lower TNFR1 Levels Correlate with Better Outcomes

Graft-versus-host disease (GVHD) causes most non-relapse mortality (NRM) after alternative donor (unrelated and mismatched related) hematopoietic cell transplant (HCT). We previously showed that increases in day +7 TNF-receptor-1 (TNFR1) ratios (posttransplantation day +7/pretransplantation baseline) after myeloablative HCT correlate with outcomes including GVHD, NRM, and survival. Therefore, we conducted a phase II trial at 2 centers, testing whether the addition of the TNF-inhibitor etanercept (25 mg twice weekly from start of conditioning to day +56) to standard GVHD prophylaxis would lower TNFR1 levels, reduce GVHD rates, and improve NRM and survival. Patients underwent myeloablative HCT from a matched unrelated donor (URD; N = 71), 1-antigen mismatched URD (N = 26), or 1-antigen mismatched related donor (N = 3) using either total body irradiation (TBI)-based conditioning (N = 29) or non-TBI-based conditioning (N = 71). Compared to historical controls, the increase in posttransplantation day +7 TNFR1 ratios was not altered in patients who received TBI-based conditioning, but was 40% lower in patients receiving non-TBI-based conditioning. The latter group experienced relatively low rates of severe grade 3 to 4 GVHD (14%), 1-year NRM (16%), and high 1-year survival (69%). These findings suggest that (1) the effectiveness of TNF-inhibition with etanercept may depend on the conditioning regimen, and (2) attenuating the expected rise in TNFR1 levels early posttransplantation correlates with good outcomes.     

Phenolic content, antioxidant effect and cytotoxic activity of Leea indica leaves

ABSTRACT: BACKGROUND: The leaves of Leea indica (Vitaceae), commonly known as 'Huo Tong Shu' in Malaysia, have been traditionally used as natural remedy in folk medicine by the locals. The current study reports the outcome of antioxidant and cytotoxic investigation of L. indica leaves. To the best of our knowledge, this is the first report of L. indica leaf crude ethanol and its fractionated extracts (hexane, ethyl acetate and water) for evaluation of total phenolic content, antioxidant effect and cytotoxic activity against colon cancer cell lines. METHODS: In the present study, L. indica leaf crude ethanol and its fractionated extracts (hexane, ethyl acetate and water) were firstly prepared prior to phenolic content, antioxidant effect and cytotoxic activity assessment. Folin-Ciocalteau's method was used for the measurement of total phenolic content of the extracts. The antioxidant activity was measured by employing three different established testing systems, such as scavenging activity on DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals, reducing power assay and SOD (superoxide dismutase) activity assay. The cytotoxic activity of the extracts were evaluated against three colon cancer cell lines with varying molecular characteristics (HT-29, HCT-15 and HCT-116) by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. RESULTS: The total phenolic content and antioxidant capabilities differed significantly among the L. indica leaf extracts. A strong correlation between total phenolic content and antioxidant properties was found, indicating that phenolic compounds are the major contributor to the antioxidant properties of these extracts. Among the crude ethanol and its fractionated extracts, fractionated water extract showed significantly the highest total phenolic content and strongest antioxidant effect in all the antioxidant testing systems employed in this study. All the four extracts exert no damage to the selected colon cancer cells. CONCLUSIONS: The data obtained in these testing systems clearly establish the antioxidant potency of the fractionated water extract of L. indica leaves. Additional studies should be carried out to isolate and identify the bioactive compounds in the fractionated water extract, in order to provide more convincing evidence.     

Fulminant and Fatal Multiple Organ Failure in a 12-Year-Old Boy With Mycoplasma pneumoniae Infection

Mycoplasma pneumoniae (Mp) is a unique pathogen that causes not only pulmonary but also extrapulmonary manifestations that must be rapidly diagnosed. A 12-year-old boy, with no relevant medical history, presented with fever, severe epigastric pain, and vomiting. Laboratory findings showed fulminant and cholestatic hepatitis, hemolytic anemia, thrombocytopenia, acute kidney injury, disseminated intravascular coagulopathy, acute myocardial infarction, and rhabdomyolysis. His clinical condition rapidly deteriorated during intubation and continuous renal replacement therapy. Despite intensive treatment, he did not recover. We report a case of fulminant and fatal multiple organ failure in a previously healthy boy with Mp infection, describing the possible pathomechanisms of multiple organ failure involved in the disease.     

AMPK activation reduces vascular permeability and airway inflammation by regulating HIF/VEGFA pathway in a murine model of toluene diisocyanate-induced asthma

Background

Occupational asthma is characterized by airway inflammation and hyperresponsiveness associated with increased vascular permeability. AMP-activated protein kinase (AMPK) has been suggested to be a novel signaling molecule modulating inflammatory responses.

Objective

We sought to evaluate the involvement of AMPK in pathogenesis of occupational asthma and more specifically investigate the effect and molecular mechanisms of AMPK activation in regulating vascular permeability.

Methods

The mechanisms of action and therapeutic potential of an AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) were tested in a murine model of toluene diisocyanate (TDI)-induced asthma.

Results

AICAR attenuated airway inflammation and hyperresponsiveness increased by TDI inhalation. Moreover, TDI-induced increases in levels of hypoxia-inducible factor (HIF)-1α, HIF-2α, vascular endothelial growth factor A (VEGFA), and plasma exudation were substantially decreased by treatment with AICAR. Our results also showed that VEGFA expression was remarkably reduced by inhibition of HIF-1α and HIF-2α with 2-methoxyestradiol (2ME2) and that an inhibitor of VEGFA activity, CBO-P11 as well as 2ME2 significantly suppressed vascular permeability, airway infiltration of inflammatory cells, and airway hyperresponsiveness induced by TDI. In addition, AICAR reduced reactive oxygen species (ROS) generation and levels of malondialdehyde and T-helper type 2 cytokines (IL-4, IL-5, and IL-13), while this agent enhanced expression of an anti-inflammatory cytokine, IL-10.

Conclusions

These results suggest that AMPK activation ameliorates airway inflammatory responses by reducing vascular permeability via HIF/VEGFA pathway as well as by inhibiting ROS production and thus may be a possible therapeutic strategy for TDI-induced asthma and other airway inflammatory diseases.     

Vaccine-elicited 10-kilodalton culture filtrate protein-specific CD8+ T cells are sufficient to mediate protection against Mycobacterium tuberculosis infection

The 10-kDa culture filtrate protein (CFP-10) and 6-kDa early secretory antigen of T cells (ESAT-6) are secreted in abundance by Mycobacterium tuberculosis and are frequently recognized by T cells from infected people. The genes encoding these proteins have been deleted from the genome of the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin (BCG), and it is hypothesized that these proteins are important targets of protective immunity. Indeed, vaccination with ESAT-6 elicits protective CD4+ T cells in C57BL/6 mice. We have previously shown that M. tuberculosis infection of C3H mice elicits CFP-10-specific CD8+ and CD4+ T cells. Here we demonstrate that immunization with a CFP-10 DNA vaccine stimulates a specific T-cell response only to the H-2K(k)-restricted epitope CFP-10(32-39). These CFP-10(32-39)-specific CD8+ cells undergo a rapid expansion and accumulate in the lung following challenge of immunized mice with aerosolized M. tuberculosis. Protective immunity is induced by CFP-10 DNA vaccination as measured by a CFU reduction in the lung and spleen 4 and 8 weeks after challenge with M. tuberculosis. These data demonstrate that CFP-10 is a protective antigen and that CFP-10(32-39)-specific CD8+ T cells elicited by vaccination are sufficient to mediate protection against tuberculosis.