Continuing perioperative estrogen therapy does not increase venous thromboembolic events in transgender patients: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to compare the risk of venous thromboembolic events (VTE) between patients suspending and continuing estrogen therapy perioperatively, in male to female gender-affirming surgery (vaginoplasty). MATERIALS AND METHODS: The authors conducted a systematic review and meta-analysis of existing research on male to female gender-affirming study, which compared the risk of VTE among the usage of estrogen perioperatively. RESULTS: A total of 209 studies were identified as potentially eligible among PubMed, Embase, and Cochrane library databases. Among the studies, 191 studies were excluded due to their abstract inappropriateness. Out of the remaining 18 studies, only 3 articles were eligible and were finally included. Meta-analysis was performed and showed odds ratio of 0.77 (95% CI: 0.04, 14.01). CONCLUSIONS: Perioperative estrogen therapy does not increase VTE risk on male to female gender-affirming surgery. Therefore, estrogen therapy may be continued perioperatively in vaginoplasty. More prospective studies are needed.

Morphological Study of Poly(vinylbenzyl chloride)-Grafted Poly(ethylene-co-tetrafluoroethylene) [ETFE-g-PVBC] Films Using Small-Angle Neutron Scattering Analysis.

In this study, the effect of degree of the grafting and crosslinking on the morphology of the crystalline domain in poly(vinylbenzyl chloride)-grafted poly(ethylene-co-tetrafluoroethylene) [ETFE-g-PVBC] films was investigated using a SANS (small-angle neutron scattering) analysis. The grafted films can be used as a precursor for ion-exchange membrane. ETFE-g-PVBC films with various degrees of cross-linking were prepared by a simultaneous irradiation grafting of vinylbenzyl chloride (VBC) and divinylbenzene (DVB) onto an ETFE film. The SEM-EDX (scanning electron microscopy-energy dispersive X-ray spectroscopy) results of a cross-sectional distribution of ETFE-g-PVBC films showed that the chlorine atoms were well-distributed throughout the films. SANS profiles of the PVBC-grafted films in the absence of a DVB crosslinker showed that the crystalline domain peaks were observed and the peak maximum position shifted significantly from 0.032 Å-(-1) to 0.02 Å(-1) with an increase in the degree of grafting. However, peak maximum positions of the PVBC-grafted films in the presence of a DVB crosslinker shifted slightly from 0.02 Å(-1) to 0.024 Å(-1) with an increase in the amount of DVB monomer at same degree of grafting. These results indicate that the degree of grafting and crosslinking affect the morphology of the crystalline domain in the ETFE-g-PVBC films.

Factors associated with development of late significant tricuspid regurgitation after successful left-sided valve surgery.

BACKGROUND: Persistent significant tricuspid regurgitation (TR) after successful left-sided valve surgery is frequently reported. OBJECTIVES: To evaluate the incidence, risk factors and clinical impact of development of late significant TR after successful left-sided valve surgery. METHODS AND RESULTS: 638 patients (356 men, mean age 52 (SD 14) years) who had mild (or=3/4 at follow-up echocardiography. Clinical events were defined as cardiovascular death, repeated open-heart surgery, and congestive heart failure requiring hospital admission. The overall incidence of late significant TR was 7.7% (49/638). Age (hazard ratio (HR), 1.0, 95% CI, 1.0 to 1.1; p = 0.005), female gender (HR, 5.0; 95% CI 2.0 to 12.7; p = 0.001), rheumatic aetiology (HR, 3.8; 95% CI 1.4 to 10.3; p = 0.011), atrial fibrillation (Af) (HR, 2.6; 95% CI 1.1 to 6.4; p = 0.035) and peak pressure gradient of TR at follow-up (HR, 1.1; 95% CI 1.0 to 1.1; p<0.001) were independent factors associated with development of late significant TR. During clinical follow-up of 101 (24) months, patients who developed late significant TR showed a significantly lower 8-year clinical event-free survival rate (76 (6) vs 91 (1)%, p<0.001). CONCLUSIONS: Several clinical variables were independent risk factors for development of late significant TR. Early surgical intervention for TR in selected patients with these risk factors may be justified, even though they have only mild TR.

Quality of life outcomes following laparoscopic total mesorectal excision for low rectal cancers: a clinical control study.

AIMS: To evaluate the health-related quality of life (HRQoL) outcomes in patients undergoing laparoscopic total mesorectal excision (LTME) with anal sphincter preservation (ASP) for low rectal cancers. METHODS: Patients undergoing LTME with ASP or open procedures (OTME) for low rectal cancers were prospectively followed up. All patients were treated in curative attempt and were free of local recurrence during the study. HRQoL was assessed by questionnaires during 3-6 months, 12-18 months, and 2-5 years after surgery. RESULTS: From June 2001 to March 2006, 125 patients undergoing LTME and 103 undergoing OTME were included in this study. In contrast to OTME patients, the LTME ones showed significantly better physical function during 3-6 months after surgery, less micturition problems within 12-18 months, less male sexual problems and better sexual function during 12-18 months after surgery, with better sexual enjoyment after 24 months postoperatively. Both groups showed significant improvement in most subscales from the first to the second assessment, and an improvement in sexual enjoyment from the second to the third assessment. The sexual function, micturition problems and male sexual problems in the LTME group significantly improved from the first to the second assessment, whereas the sexual function in the OTME group improved from the second to the third assessment. CONCLUSIONS: Patients undergoing LTME for low rectal cancers can achieve superior postoperative HRQoL than patients undergoing OTME, with superior physical function, micturition function, overall sexual and male sexual functions in the short term, and better sexual enjoyment in the long term. The HRQoL of both LTME and OTME patients may be expected to improve over time, particularly over the first postoperative year.

Roles of NF-kappaB and bcl-2 in two differential modes of cell death of mouse cortical collecting duct cells.

Recent data have implicated nuclear factor-kappaB (NF-kappaB) and Bcl-2 in the regulation of apoptotic and necrotic cell death in various cells. However, mechanisms of their effects on cell death of renal epithelial cells are not clear. First, we investigated the effect of specific inhibition of NF-kappaB and overexpression of Bcl-2 on necrotic cell death induced by hydrogen peroxide or cisplatin in renal collecting duct cells. M-1 cells, which were derived from outer cortical collecting duct, were stably transfected with the non-phosphorylatable mutant of inhibitory-kappaBalpha (I-kappaBalpha) and Bcl-2. Overexpression of I-kappaBalpha and Bcl-2 did not affect cisplatin-induced necrotic cell death, but overexpression of I-kappaBalpha significantly decreased H2O2-induced cell death. Regarding apoptotic cell death induced by cisplatin, serum deprivation and contact inhibition was increased by overexpression of I-kappaBalpha, whereas overexpression of bcl-2 inhibited the apoptotic cell death. I-kappaBalpha overexpression increased Bax expression and decreased cIAP-1 and -2 expression compared to vector-transfected cells, but did not alter SAPK/JNK activity in the presence or absence of cisplatin. NF-kappaB activity was significantly higher in bcl-2-overexpressing cells than in control cells. These data show that activation of NF-kappaB mediates H2O2-induced necrotic injury, but inhibits apoptotic cell death in renal collecting duct cells, and that Bcl-2 selectively protects apoptotic cell death in M-1 cells.

Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis.

In this work, the development and applications of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo disease diagnosis including oral carcinoma are described. The optical diagnosis system was based on an OPO laser for multi-wavelength excitation and time-resolved detection. The pulsed Nd-YAG-pumped OPO laser system (6 ns, 20 Hz) is compact and has a rapid, broad, and uniform tuning range. Time-gated detection of intensified charge-coupled device (ICCD) making use of external triggering was used to effectively eliminate the laser scattering and contribute to the highly sensitive in vivo measurements. Artificial tissue-simulating phantoms consisting of polystyrene microspheres and tissue fluorophores were tested to optimize the gating parameters. 51-ns gate width and 39-ns gate delays were determined to be the optimal parameters for sensitive detection. In vivo measurements with the optical diagnosis system were applied to esophagus, stomach, and small intestine using an endoscope in canine animal studies. The rapid tuning capability of the optical diagnosis system contributed greatly to the optimization of wavelength for the observation of porphyrin in the small intestine. When the small intestine was thoroughly washed with water, the emission band which corresponds to porphyrin disappeared. Based on this observation, it was concluded that the detected signal was yielded by porphyrin-containing bile secretion. Also, multispectral analyses using multiple excitations from 415 to 480 nm at 5 nm intervals confirmed the porphyrin detection in the small intestine. The optical diagnosis system was also applied to the detection of human xenograft of oral carcinoma in mice using 5-aminolevulinic acid (5-ALA) which is a photodynamic therapy (PDT) drug. Significant differences in protoporphyrin IX fluorescence intensity between normal and tumor tissue could be obtained 2 hours after the injection of 5-ALA into mice due to the preferential accumulation of 5-ALA in tumors. Results reported herein demonstrate potential capabilities of the LIF-OPO system for in vivo disease diagnosis.

Atrial fibrillation surgery simplified with cryoablation to improve left atrial function.

BACKGROUND: The Maze procedure restores atrial fibrillation to normal sinus rhythm. However, concurrent left atrial functional recovery is not always achieved. To address this limitation, a modification using linear cryoablation is described. METHODS: Between July 1997 and December 1999, 83 patients received atrial fibrillation surgery in association with mitral valve surgery with or without additional concurrent procedures by either the conventional technique, group I (n = 30) or the modified technique, group II (n = 53). Onset of sinus conversion and echocardiographic assessment of postoperative left ventricular function, left atrial size, and mitral A-wave velocity were compared in the early postoperative period and 6 months after surgery. RESULTS: Sinus conversion occurred significantly earlier in group II, 2.4 +/- 5 days versus group I, 7.0 +/- 10 days. The mean transmitral A-wave velocity and the incidence of A-wave appearance in the early postoperative period and 6 months postoperatively were greater in group II than group I. CONCLUSIONS: With the current modification, restoration of sinus rhythm and superior left atrial contractile function occurred earlier than with the standard Maze III technique.

Clinical characteristics of constrictive pericarditis diagnosed by echo-Doppler technique in Korea.

A retrospective analysis of clinical data of 71 patients with constrictive pericarditis (CP) diagnosed by echo-Doppler technique (mean age, 49+/-17) was done. In 27 patients (38%), the etiology was unknown, and the three most frequent identifiable causes were tuberculosis (23/71, 32%), cardiac surgery (8/71, 11%), and mediastinal irradiation (6/71, 9%). Pericardiectomy was performed in 35 patients (49%) with a surgical mortality of 6% (2/35), and 11 patients (15%, 11/ 71) showed complete resolution of constrictive physiology with medical treatment. Patients with transient CP were characterized by absence of pericardial calcification, shorter symptom duration, and higher incidence of fever, weight loss, and tuberculosis. The 5-yr survival rates of patients with transient CP and those undergoing pericardiectomy were 100% and 85+/-6%, respectively, which were significantly higher than that of patients without undergoing pericardiectomy (33+/-17%, p=0.0083). Mediastinal irradiation, higher functional class, low voltage in ECG, low serum albumin, and old age were the independent variables associated with a higher mortality. Tuberculosis is still the most important etiology of CP in Korea, and not infrequently, it may cause transient CP. Early diagnosis and decision-making using follow-up echocardiography are crucial to improve the prognosis of patients with CP.

Intravascular ultrasound analysis of beta radiation therapy for diffuse in-stent restenosis to inhibit intimal hyperplasia.

We evaluated the efficacy of beta-radiation therapy ((188)Re-MAG(3)) to inhibit intimal hyperplasia (IH) in diffuse in-stent restenosis by intravascular ultrasound (IVUS) analysis in 50 patients. Nine patients who did not agree with radiation therapy, and therefore underwent rotational atherectomy and balloon angioplasty for diffuse in-stent restenosis in the same study period, were selected for control groups. Serial IVUS comparisons were available in 44 of 50 patients with radiation therapy and 7 of 9 control patients. At 6-month follow-up, there was less significant increase of IH area in patients with radiation therapy than in control patients (Delta IH area = 0.1 +/- 0.8 mm(2) vs. 2.6 +/- 1.8 mm(2), P > 0.001 in mean values, and 0.6 +/- 1.4 mm(2) vs. 2.9 +/- 2.1 mm(2), P = 0.026 in values of follow-up lesion site, respectively). In conclusion, beta-radiation therapy might be an effective treatment modality to inhibit intimal hyperplasia in patients with diffuse in-stent restenosis.

Cisplatin-induced apoptosis by translocation of endogenous Bax in mouse collecting duct cells.

cis-platinum(II) (cis-diammine dichloroplatinum; cisplatin) is a potent antitumor compound that is widely used for the treatment of many malignancies. An important side-effect of cisplatin is nephrotoxicity, which results from injury to renal tubular epithelial cells and can be manifested as either acute renal failure or a chronic syndrome characterized by renal electrolyte wasting. Recently, apoptosis has been recognized as an important mechanism of cell death mediating the antitumor effect of cisplatin. This study was undertaken to examine the mechanisms of cell death induced by cisplatin in M-1 cells, which were derived from the outer cortical collecting duct cells of SV40 transgenic mice. Treatment of M-1 cells with high concentrations of cisplatin (0.5 and 1 mM) for 2 hr led to necrotic cell death, whereas a 24-hr treatment with 5-20 microM cisplatin led to apoptosis. Antioxidants protected against cisplatin-induced necrosis, but not apoptosis, indicating that reactive oxygen species play a role in mediating necrosis but not apoptosis induced by cisplatin and that the mechanism of cell death induced by cisplatin is concentration dependent. The low concentrations of cisplatin, which induced apoptosis in M-1 cells, did not affect the expression levels of Bcl-2-related proteins and did not activate c-Jun NH2-terminal kinase (SAPK/JNK). Cisplatin induced the translocation of endogenous Bax from the cytosolic to the membrane fractions and, subsequently, the release of cytochrome c. Overexpression of Bcl-2 blocked cisplatin-induced apoptosis and Bax translocation. These observations suggest that the subcellular redistribution of Bax is a critical event in the apoptosis induced by cisplatin.

Optimization of DNA electrophoretic behavior in poly(vinyl pyrrolidone) sieving matrix for DNA sequencing.

Poly(vinyl pyrrolidone) solution was used as a separation matrix in capillary electrophoresis for DNA sequencing. Four-label four-color detection was performed for base calling. Dye-labeled DNA showed large mobility shifts at normal conditions for DNA separation. Temporal correction of mobility shifts was achieved by normalizing with respect to pure peaks that are without spectral interference or temporal overlap at each color channel. To achieve even better performance, a DNA separation condition that does not require corrections for mobility shifts was found. Dichlororhodamine-labeled DNA fragments showed ideal electrophoretic behaviors according to DNA size in the presence of 10 M urea. The base-calling accuracy of dichlororhodamine-labeled M13mp18 and PGEM/U DNA were 99.3% for 333 bases and 99% for 315 bases, respectively. Base calling of unknown DNA samples obtained in the presence of 10 M urea showed 99.1% accuracy.

Effect of hypercholesterolemia on macrophage infiltration after balloon injury to rabbit iliac artery.

Both hypercholesterolemia and vascular injury have been reported to induce macrophage infiltration, but their combined effect and the mechanism by which hypercholesterolemia enhances the infiltration remain to be clarified in vivo. To evaluate the effect of hypercholesterolemia on macrophage infiltration after vascular injury, the iliac arteries of hypercholesterolemic (HC) and normocholesterolemic (NC) rabbits were examined 2h, 1 day, 3 days, 7 days, and 14 days after balloon injury using immunohistochemical staining for macrophages, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1. Nuclear factor kappa-B (NF-kappaB) activation was also evaluated in fresh frozen iliac arteries using the electrophoretic mobility shift assay method. The fundamental difference between HC and NC was the amount of macrophage infiltration seen in HC from 7 days after balloon injury. Two out of 4 HC iliac arteries on the 7th day, and 3 out of 4 HC iliac arteries on the 14th day were positively stained with ICAM-1 in regenerated endothelium and neointima, whereas there were no positively stained NC iliac arteries. Neither HC nor NC tissues showed positive staining with VCAM-1. NF-kappaB was activated in HC 7 and 14 days after balloon injury, but not in NC. In conclusion, in vivo hypercholesterolemia induces macrophage infiltration after balloon injury and it is mediated by increased NF-kappaB activation promoting ICAM-1 expression.

Variant angina is not associated with angiotensin I converting enzyme gene polymorphism but rather with smoking.

BACKGROUND: Angiotensin converting enzyme (ACE) perhaps plays roles in regulating coronary vasomotor tone by producing angiotensin II and degrading bradykinin. OBJECTIVES: We sought to investigate the role of ACE gene polymorphism in the pathogenesis of variant angina and to compare it with that of other clinical risk factors for male patients with variant angina and age-matched and sex-matched control subjects. METHODS: We studied 78 male patients with variant angina who exhibited spontaneous or provoked coronary spasms during coronary angiography and compared prevalences of ACE gene genotype (deletion D and insertion I) and other risk factors between this group of patients with variant angina and age-matched and sex-matched control subjects whose angiograms were normal and in whom the ergonovine test did not cause spasms (n = 80). RESULTS: Smokers were more prevalent in the group of patients with variant angina (P < 0.05). Genotype and allele prevalences of the group of patients with variant angina (0.14, 0.53 and 0.33 for DD, DI and II and 0.41 and 0.59 for D and I, respectively) were no different from those of the control group (0.16, 0.49 and 0.35 for DD, DI and II and 0.40 and 0.60 for D and I). Multiple logistic regression analysis showed that smoking was a significant risk factor for variant angina (odds ratio 2.61, 95% confidence interval 1.03-6.66) whereas ACE genotype was not. CONCLUSIONS: Variant angina is associated with an environmental factor, such as smoking, rather than a genetic factor, such as ACE gene polymorphism.

Evidence of genetic progression in human gastric carcinomas with microsatellite instability.

Mutator phenotype tumors provide unique opportunities to unravel malignant progression because of various gene alterations acquired during clonal tumor evolution. Gastric carcinomas, which have been known to show frequent genetic instability, would be composed of initial gene alterations shared by most tumor areas and subsequent alterations restricted to particular tumor sites. To analyse the timing of genetic events, we examined separate sites of tumor tissue obtained from a given gastric carcinoma patient with microsatellite instability (MSI). Our study included 95 normal/tumor area pairs from 25 patients. Six of the 25 patients (24%) demonstrated various levels of MSI ranging from 7% (two of 30) to 97% (28 of 29) of markers tested in multiple tumor sites. Of the six patients, five manifested frameshift mutations in a tract of ten deoxyadenosines within transforming growth factor beta receptor type II and four demonstrated frameshift mutations in a tract of eight deoxyguanosines within BAX. These mutations were common to all tumor sites regardless of the various level of MSI phenotype, indicating initial events. Two of the six patients exhibited frameshift mutations in mononucleotide repeats of mismatch repair genes, hMSH3 and hMSH6, and the insulin-like growth factor II receptor in restricted tumor areas, indicating additional alterations. Insulin-like growth factor II receptor mutations appear to be caused by hMSH3 and hMSH6 mutations because the former mutations were confined to tumor portions with the latter two mismatch repair lesions. These results provide genetic progression evidence for gastric carcinomas of the mutator pathway. In this pathway, mismatch repair insufficiency initially targets mononucleotide tracts of transforming growth factor beta receptor type II and BAX. During tumorigenesis, primary mismatch repair failure may give rise to the secondary mismatch repair lesions, frameshift mutations of hMSH3 and hMSH6, which result in another tumorigenic mutation in the insulin-like growth factor II receptor.