Centrally Reduced Diffusion Sign for Differentiation between Treatment-Related Lesions and Glioma Progression: A Validation Study.

BACKGROUND AND PURPOSE: Differentiating between treatment-related lesions and tumor progression remains one of the greatest dilemmas in neuro-oncology. Diffusion MR imaging characteristics may provide useful information to help make this distinction. The aim of the study was to assess the diagnostic accuracy of the centrally reduced diffusion sign for differentiation of treatment-related lesions and true tumor progression in patients with suspected glioma recurrence. MATERIALS AND METHODS: The images of 231 patients who underwent an operation for suspected glioma recurrence were reviewed. Patients with susceptibility artifacts or without central necrosis were excluded. The final diagnosis was established according to histopathology reports. Two neuroradiologists classified the diffusion patterns on preoperative MR imaging as the following: 1) reduced diffusion in the solid component only, 2) reduced diffusion mainly in the solid component, 3) no reduced diffusion, 4) reduced diffusion mainly in the central necrosis, and 5) reduced diffusion in the central necrosis only. Diagnostic accuracy metrics and the area under the receiver operating characteristic curve were estimated for the diffusion patterns. RESULTS: One hundred three patients were included (22 with treatment-related lesions and 81 with tumor progression). The diagnostic accuracy results for the centrally reduced diffusion pattern as a predictor of treatment-related lesions ("mainly central" and "exclusively central" patterns versus all other patterns) were as follows: 64% sensitivity (95% CI, 41%-83%), 84% specificity (95% CI, 74%-91%), 52% positive predictive value (95% CI, 37%-66%), and 89% negative predictive value (95% CI, 83%-94%). CONCLUSIONS: The centrally reduced diffusion sign is associated with the presence of treatment effect. The probability of a histologic diagnosis of a treatment-related lesion is low (11%) in the absence of centrally reduced diffusion.

Anisotropic dependence of light extraction behavior on propagation path in AlGaN-based deep-ultraviolet light-emitting diodes.

The anisotropic extraction dependence of polarized light on propagation path in AlGaN-based deep-ultraviolet (DUV) light-emitting diodes (LEDs) is investigated by simulations and photoluminescence (PL) measurements. Theoretical calculations based on k⋅p approximation and Monte Carol ray tracing indicate that there are two kinds of polarized sources with different angular distributions in ~280 nm AlGaN-based LEDs, s-polarized (spherical-shaped) and p-polarized (dumbbell-shaped) sources, which have different extraction behaviors. It is found that the total light extraction intensities are improved with decreasing the propagation path, and the lateral surface extraction gradually becomes dominant. Moreover, the extraction intensity of s-polarized light improves more than that of p-polarized light when the propagation path decreases, leading to a greater polarization degree. Polarization-resolved PL measurements show that the polarization degree of extracted light from lateral facet of the AlGaN multiple quantum well sample can be enhanced from 1% to 17% as the average propagation path reduces by 0.6 mm, which is consistent with the simulation results of the anisotropic dependence of light extraction on propagation path. Our results are significant for understanding and modulating the anisotropic extraction behavior of polarized light to realize high efficiency AlGaN-based DUV LEDs.

CYP4A in tumor-associated macrophages promotes pre-metastatic niche formation and metastasis.

Tumor-associated macrophages (TAMs) play an essential role in metastasis. However, what enables TAMs to have a superior capacity to establish pre-metastatic microenvironment in distant organs is unclear. Here we have begun to uncover the effects of cytochrome P450 (CYP) 4A in TAMs on lung pre-metastatic niche formation and metastasis. CYP4A+ TAM infiltration was positively associated with metastasis, pre-metastatic niche formation and poor prognosis in breast cancer patients. The pharmacological inhibition of CYP4A reduced lung pre-metastatic niche formation (evidenced by a decrease in vascular endothelial growth factor receptor 1 positive (VEGFR1+) myeloid cell recruitment and pro-metastatic protein expression) and metastatic burden, accompanied with TAM polarization away from the M2 phenotype in spontaneous metastasis models of 4T1 breast cancer and B16F10 melanoma. Co-implantation of 4T1 cells with CYP4A10high macrophages promoted lung pre-metastatic niche formation and metastasis. Depletion of TAMs disrupted lung pre-metastatic niches and thereby prevented metastasis. Treatment with the CM from CYP4A10high M2 macrophages (M2) increased pre-metastatic niche formation and metastatic burden in the lungs, whereas CYP4A inhibition attenuated these effects. In vitro TAM polarization away from the M2 phenotype induced by CYP4A inhibition decreased VEGFR1+ myeloid cell migration and fibronectin expression, accompanied with downregulation of STAT3 signaling. Conversely, overexpression of CYP4A or exogenous addition of 20-hydroxyeicosatetraenoic acid promoted M2 polarization and cytokine production of macrophages and thereby enhanced migration of VEGFR1+ myeloid cells, which were reversed by siRNA or pharmacological inhibition of STAT3. Importantly, a combined blocking M2 macrophage-derived factors TGF-ß, VEGF and SDF-1 abolished VEGFR1+ myeloid cell migration and fibroblast activation induced by CYP4A. In summary, CYP4A in TAMs is crucial for lung pre-metastatic niche formation and metastasis, and may serve as a potential therapeutic target in human cancer.

Loss of serum response factor induces microRNA-mediated apoptosis in intestinal smooth muscle cells.

Serum response factor (SRF) is a transcription factor known to mediate phenotypic plasticity in smooth muscle cells (SMCs). Despite the critical role of this protein in mediating intestinal injury response, little is known about the mechanism through which SRF alters SMC behavior. Here, we provide compelling evidence for the involvement of SRF-dependent microRNAs (miRNAs) in the regulation of SMC apoptosis. We generated SMC-restricted Srf inducible knockout (KO) mice and observed both severe degeneration of SMCs and a significant decrease in the expression of apoptosis-associated miRNAs. The absence of these miRNAs was associated with overexpression of apoptotic proteins, and we observed a high level of SMC death and myopathy in the intestinal muscle layers. These data provide a compelling new model that implicates SMC degeneration via anti-apoptotic miRNA deficiency caused by lack of SRF in gastrointestinal motility disorders.

Capability of GaN based micro-light emitting diodes operated at an injection level of kA/cm².

Different size InGaN/GaN based micro-LEDs (µLEDs) are fabricated. An extremely high injection level above 16 kA/cm2 is achieved for 10 µm-diameter LED. The lateral current density and carrier distributions of the µLEDs are simulated by APSYS software. Streak camera time resolved photoluminescence (TRPL) results show clear evidence that the band-gap renormalization (BGR) effect is weakened by strain relaxation in smaller size µLEDs. BGR affects the relaxation of free carriers on the conduction band bottom in multiple quantum wells (MQWs), and then indirectly affects the recombination rate of carriers. An energy band model based on BGR effect is made to explain the high-injection-level phenomenon for µLEDs.

Laser-driven proton acceleration enhancement by nanostructured foils.

Nanostructured thin plastic foils have been used to enhance the mechanism of laser-driven proton beam acceleration. In particular, the presence of a monolayer of polystyrene nanospheres on the target front side has drastically enhanced the absorption of the incident 100 TW laser beam, leading to a consequent increase in the maximum proton energy and beam charge. The cutoff energy increased by about 60% for the optimal spheres' diameter of 535 nm in comparison to the planar foil. The total number of protons with energies higher than 1 MeV was increased approximately 5 times. To our knowledge this is the first experimental demonstration of such advanced target geometry. Experimental results are interpreted and discussed by means of 2(1/2)-dimensional particle-in-cell simulations.

Ion spectrometer composed of time-of-flight and Thomson parabola spectrometers for simultaneous characterization of laser-driven ions.

An ion spectrometer, composed of a time-of-flight spectrometer (TOFS) and a Thomson parabola spectrometer (TPS), has been developed to measure energy spectra and to analyze species of laser-driven ions. Two spectrometers can be operated simultaneously, thereby facilitate to compare the independently measured data and to combine advantages of each spectrometer. Real-time and shot-to-shot characterizations have been possible with the TOFS, and species of ions can be analyzed with the TPS. The two spectrometers show very good agreement of maximum proton energy even for a single laser shot. The composite ion spectrometer can provide two complementary spectra measured by TOFS with a large solid angle and TPS with a small one for the same ion source, which are useful to estimate precise total ion number and to investigate fine structure of energy spectrum at high energy depending on the detection position and solid angle. Advantage and comparison to other online measurement system, such as the TPS equipped with microchannel plate, are discussed in terms of overlay of ion species, high-repetition rate operation, detection solid angle, and detector characteristics of imaging plate.

Risk factors of mortality for nosocomial pneumonia: importance of initial anti-microbial therapy.

Nosocomial pneumonia is a common nosocomial infection and has high mortality rate. Risk factors of mortality of nosocomial pneumonia were studied in 132 hospitalised patients who developed nosocomial pneumonia. The overall mortality rate was 64/132, 48.5%. Of the 11 risk factors univariately associated with mortality due to nosocomial pneumonia, only the inappropriate initial anti-microbial therapy, high simplified acute physiology score and multiple organ failures remained significant after stepwise logistic regression. Gram-negative bacilli were still the most pre-dominant causative microbiologic agents of nosocomial pneumonia with Pseudomonas aeruginosa (20.3%), Acinetobacter baumannii (18.6%) and Escherichia coli (5.9%) being the three most predominant pathogens. A. baumannii were significantly more predominant among non-survivors than survivors (13.56 vs. 5.08%, p=0.0418). The incidence rate of methicillin-resistant Staphylococcus aureus was 19.5% higher than previous reports. We conclude that inappropriate initial anti-microbial therapy for nosocomial pneumonia is associated with the mortality rate of nosocomial pneumonia, and appropriate anti-microbial therapy improves outcome of nosocomial pneumonia.

Gene therapy for bladder pain with gene gun particle encoding pro-opiomelanocortin cDNA.

PURPOSE: Interstitial cystitis is a bladder hypersensitivity disease associated with bladder pain that has been a major challenge to understand and treat. We hypothesized that targeted and localized expression of endogenous opioid peptide in the bladder could be useful for the treatment of bladder pain. Pro-opiomelanocortin (POMC) is one of such precursor molecules. In this study we developed a gene gun method for the transfer of POMC cDNA in vivo and investigated its therapeutic effect on acetic acid induced bladder hyperactivity in rats. MATERIALS AND METHODS: Human POMC cDNA was cloned into a modified pCMV plasmid and delivered into the bladder wall of adult female rats by direct injection or the gene gun. Three days after gene therapy continuous cystometrograms were performed using urethane anesthesia by filling the bladder (0.08 ml per minute) with saline, followed by 0.3% acetic acid. Bladder immunohistochemical testing was used to detect endorphin after POMC cDNA transfer. RESULTS: The intercontraction interval was decreased after intravesical instillation of acetic acid (73.1% or 68.1% decrease) in 2 control groups treated with saline or the gene gun without POMC cDNA, respectively. However, rats that received POMC cDNA via the gene gun showed a significantly decreased response (intercontraction interval 35% decreased) to acetic acid instillation, whereas this antinociceptive effect was not detected in the plasmid POMC cDNA direct injection group. This effect induced by POMC gene gun treatment was reversed by intramuscular naloxone (1 mg/kg), an opioid antagonist. Increased endorphin immunoreactivity with anti-endorphin antibodies was observed in the bladder of gene gun treated animals. CONCLUSIONS: The POMC gene can be transferred in the bladder using the gene gun and increased bladder expression of endorphin can suppress nociceptive responses induced by bladder irritation. Thus, POMC gene gun delivery may be useful for the treatment of interstitial cystitis and other types of visceral pain.

Diagnostic value of serum transferrin receptor and glycosylated hemoglobin on hemolytic anemia.

Soluble serum transferritin receptor (sTfR) is a new diagnostic tool for iron depletion and erythropoiesis. Glycosylated hemoglobin (GHb) can be used to detect hemolysis. The present study was thus conducted to compare the diagnostic value of sTfR and GHb (measured as Hb A(1)c) in patients with hemolytic anemia. Four groups of subjects entered into our study. Group A included 13 patients with hemolytic anemia with effective erythropoiesis (EE). Group B included 13 patients with hemolytic anemia with ineffective erythropoiesis (IE). Group C included 15 healthy controls and group D summated groups A and B. sTfR, serum ferritin, plasma hemoglobin, complete blood count, reticulocyte, haptoglobin, lactic dehydrogenase (LDH), Hb A(1)c, liver and renal function, direct and indirect bilirubin, and fasting blood sugar were measured. Plasma Hb, hematocrit, mean corpuscular volume (MCV), platelet, haptoglobin, LDH, indirect bilirubin, Hb A(1)c, and sTfR were found to be significantly different between the controls and the hemolytics, either with effective or ineffective erythropoiesis. Reticulocyte count was significantly different only between the two hemolytic groups. Hb A(1)c and sTfR were both good for the diagnosis of hemolysis. Reticulocyte count was a good tool for distinguishing EE from IE.

Treatment guideline of enuresis in Taiwan.

The treatment guideline of enuresis suggested by the study group of enuresis in Taiwan is reported. Medical consultation and treatment of enuresis are recommended at the age of 5 and 6 years respectively. Evaluation of the enuretic children includes history taking, physical examination and laboratory investigations. A checklist is provided for quick evaluation in busy clinics. Urinalysis, urine specific gravity and office ultrasonography are essential tests. An algorithm of treatment of monosymptomatic enuresis is constructed. The two main options of treatment are behavioral modification with alarm system and pharmacotherapy with desmopressin or imipramine. Imipramine is recommended as one of the treatment options because of its relative safety in Taiwan. However the potential toxicity and mortality of imipramine is highlighted and warned. The responses to treatment are evaluated after a period of treatment for 1 to 3 months. Further evaluation and individualized treatment is suggested for poor responders.

Improvement of sexual function in male patients after parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: Clinically, the severity of uremia is known to be inversely proportional to sexual desire and activity in patients with chronic renal failure. We studied sexual function and sex hormones in male patients with symptomatic hyperparathyroidism before and 3 months after parathyroidectomy. STUDY DESIGN: From October 1998 to December 2000, 20 male patients with symptomatic secondary hyperparathyroidism were enrolled in this study. They underwent total parathyridectomy and autotransplantation of 90 mg of tissue to the subcutaneous tissue of the forearm or thigh. They all had regular sexual partners and were sexually active. Preoperatively, hemoglobin, hematocrit, calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (iPTH), prolactin, testosterone, leutenizing hormone (LH), and follicle stimulation hormone (FSH) were checked routinely. Three months after operation those data were checked again. Sexual function was evaluated with the International Index of Erectile Function (IIEF). Monthly frequency of attempted sexual intercourse, satisfaction of attempted intercourse, and enjoyment of intercourse were individually analyzed preoperatively and 3 months postoperatively. RESULTS: Hemoglobin, hematocrit, testosterone, and LH were noted to have not significantly changed 3 months after surgery. Serum levels of calcium, phosphorus, alkaline phosphatase, FSH, and iPTH were significantly reduced, as were the levels of prolactin. But preoperative and postoperative FSH levels were within normal limits, and 70% of the postoperative alkaline phosphatase levels were above normal. Sexual function increased significantly 3 months after parathyroidectomy, as did monthly frequency of attempted intercourse, satisfaction of attempted intercourse, and enjoyment of intercourse. CONCLUSIONS: Sexual function of male patients with symptomatic hyperparathyroidism can possibly be improved by parathyroidectomy and autotransplantation. Decreases in the levels of prolactin, calcium, phosphorus, and iPTH are also noticed after parathyroidectomy.

31-Year-old bladder diverticulocutaneous fistula with a giant stone as a complication of pelvic fracture.

Pelvic fractures associated with urinary bladder rupture are not rare, however, bladder fistulae are a rare complication after primary repair of bladder rupture. To our knowledge, we present the first case of a vesical diverticulocutaneous fistula after pelvic fractures. Etiology, presentation. diagnosis, and management are discussed.

Ipsilateral renal dysplasia with hypertensive heart disease in an infant with cutaneous varicella lesions: an unusual presentation of congenital varicella syndrome.

A child with congenital varicella syndrome including cutaneous lesions and ipsilateral renal dysplasia with hypertensive heart disease is described. Varicella was contracted during the tenth week of gestation. Typical congenital varicella bullae, high titer of anti-varicella-zoster virus IgM, and a small right kidney were noted after birth. Hypertensive heart disease resulting from renal dysplasia occurred at 1 year of age. The cutaneous lesions and the dysplastic kidney involved the same dermatomes. Nephrectomy proved to be the treatment of choice for hypertension and congestive heart failure.

Age related testosterone level changes and male andropause syndrome.

BACKGROUND: Much like the menopause syndrome occurring among older women, a similar condition has been defined among men. Testosterone production increases rapidly at the onset of puberty, then dwindles quickly after age 50 to become 20 to 50% of the peak level by age 80. Many men older than age 50 have experienced frailty syndrome, which includes decrease of libido, easy fatigue, mood disturbance, accelerated osteoporosis, and decreased muscle strength. We investigated serum total testosterone levels and andropause syndrome in men. METHODS: Serum total testosterone levels were measured in 53 symptomatic men older than age 50 and in 48 men younger than age 40 for a control group. We also analyzed andropause symptoms among the 53 men older than age 50. RESULTS: The mean serum total testosterone level in the symptomatic men older than age 50 (mean: 2.68 +/- 0.51 ng/ml, range: 1.21 to 4.13 ng/ml) was significantly lower than that in the control group (mean: 7.01 +/- 0.82 ng/ml, range: 5.53 ng/ml to 8.14 ng/ml). Male frailty syndrome in these men older than 50 included: decreased libido (91%), lack of energy (89%), erection problems (79%), falling asleep after dinner (77%), memory impairment (77%), loss of pubic hair (70%), sad or grumpy mood changes (68%), decrease in endurance (66%), loss of axillary hair (55%), and deterioration in work performance (51%). CONCLUSION: The serum total testosterone level showed a decline with aging, especially in the men older than age 50. Low serum testosterone levels were also associated with the symptoms of male andropause syndrome.

Surgical repair of postinfarction ventricular septal defect.

BACKGROUND: Rupture of the interventricular septum complicates 1% to 2% of all acute myocardial infarction patients and its natural course is ominous. The purpose of this study is to present our experience with surgical ventricular septal defect (VSD) repair and examine the possible risk factors and explanations for surgical mortality. METHODS: Fourteen patients underwent repair of postinfarction VSD from 1996 to 1998 at the Taipei Veterans General Hospital. Thirteen patients were in New York Heart Association (NYHA) Functional Class IV and one was in Functional Class III. Eleven patients were in cardiogenic shock with intra-aortic balloon pumps (IABPs) prior to surgery. The operative techniques for VSD repair range from extensive infarctectomy with reconstruction of the septum and the right and left ventricular free walls using single or double patches, to minimal or no infarctectomy with closure of the VSD by excluding the infarcted muscle from the left ventricular cavity and leaving the right ventricle intact. RESULTS: Overall surgical mortality occurred in four patients. All deaths occurred in patients with cardiogenic shock, two with anterior VSD and two with posterior VSD. Three late survivors had limited exercise tolerance with NYHA Functional Class II to III. Left ventricular function was moderately impaired in most patients with a mean nuclear scan ejection fraction of 0.32. However, all patients were elderly and adapted to their residual symptoms without significant life-style changes. CONCLUSIONS: The surgical mortality for treating patients with postinfarction VSD has decreased with improvements in surgical technique. Rapid diagnosis, appropriate preoperative management and delicate surgical repair improve the overall results and help to attain long-term survival.

Causes of venous thrombosis in fifty Chinese patients.

In a whole year from July 1997 to June 1998, a total of 50 patients with sonogram-proved venous thrombosis who called on our hematology clinic consecutively entered into the study. Their mean age was 59.1 +/- 17.5 years, range 18-83 years, and 29 were male. A series of examinations were performed in order to find out the cause of venous thrombosis. These examinations included antithrombin, protein C, protein S, plasminogen, heparin cofactor II, activated protein C ratio, factor V Leiden mutation, fibrinogen, factors VIII and XII, euglobulin lysis time, 677 C-->T mutation of methylenetetrahydrofolate reductase (MTHFR), prothrombin 20210 (PT 20210) A allele mutation, lupus anticoagulant, anticardiolipin antibody, and complete blood count. Five patients (10%) were found to have malignancy; an inferior vena cava thrombosis in one patient was due to venous compression by hydronephrosis; two patients had lupus anticoagulant; two had varicose veins of legs; two had protein C deficiency; four had protein S deficiency; two had plasminogen deficiency; two had antithrombin deficiency. No activated protein C resistance, elevated factor VIII level, factor V Leiden, PT 20210 A allele or heparin cofactor II deficiency was found in the present study. Homozygous MTHFR 677 C-->T gene mutation was found in 7 patients (14%); one of them also had a plasminogen deficiency. No possible risk factor of venous thrombosis could be found in 24 patients (48%). In conclusion, malignancy and protein S deficiency were the most frequent acquired and congenital causes of venous thrombosis in the Chinese, respectively.

Transmyocardial holmium-YAG laser channels in an animal model: a preliminary morphologic and histologic study.

BACKGROUND: Laser transmyocardial revascularization (TMR) appears to improve symptoms in patients with refractory angina. However, it remains a controversial treatment modality for relieving ischemia. We conducted our study in dogs and evaluated the changes in morphology and histology of the myocardium after laser TMR. METHODS: The hearts of 10 mongrel dogs (20-30 kg each) were treated with a holmiumyttrium aluminum garnet (YAG) laser in vivo. After opening the pericardium, the 1-mm fiberoptic device was used to create an average of 30 transmyocardial channels per heart at approximate intervals of 0.5 to 1 cm through normal left ventricular myocardium. All dogs tested survived the procedure. The dogs were sacrificed on the first and 60th postoperative days. RESULTS: In the day-1 postoperative group (n = 4), the transmyocardial channels were obliterated at both epicardial and endocardial ends. The channels were totally occupied by necrotic myocytes and did not appear patent under the microscope. In the day-60 postoperative group (n = 6), the epicardial and endocardial scars were identified at each original laser application site. On cross-section, the channels were invaded by fibrous tissue bands extending from the endocardium to the epicardium, without a prominent central passage. Trichrome stained specimens showed that the channels were replaced by collagen fibers, fat tissue and numerous well-developed capillaries or sinusoids in which plenty of red blood cells were found. CONCLUSIONS: We concluded that laser TMR offers no help for acute myocardial ischemia, but results in neovascularization inside the channels by the 60th postoperative day. Angiogenesis induced by laser TMR could possibly play a role in relieving chronic ischemia.

Bladder rupture after inguinal herniotomy.

An 18-month-old male sustained an extensive bladder injury during a routine right inguinal herniotomy. Primary closure of the remaining detrusor was performed. Three months postoperatively he could void spontaneously, but with a small, contracted bladder and bilateral vesicoureteral reflux. He was stable throughout a 6-month follow-up period. Further surgical options will depend upon the bladder capacity and the grade of reflux.

Minimally-invasive, direct coronary artery bypass grafting.

BACKGROUND: Minimally-invasive, direct vision coronary artery bypass grafting (MIDCAB) is a new surgical technique performed via limited thoracotomy in a beating heart without cardiopulmonary bypass. METHODS: From June 1996 to December 1996, MIDCAB was performed in 12 patients (all male, average age, 65.9 years). In 11 patients with left anterior descending coronary artery lesions, thoracotomy was performed via the left, fourth intercostal space and the pericardium was incised to identify the target site. About 8 cm of the left internal mammary artery was harvested. Bilateral anterolateral thoractomy was performed in one patient with left anterior descending and right coronary artery lesions. Anastomosis was performed under direct vision in the beating heart without cardiopulmonary bypass. RESULTS: MIDCAB was performed successfully without morbidity. The patients' average stay in the intensive care unit was 1.8 days. No patient had any early cardiac event requiring additional surgery or percutaneous transluminal coronary angioplasty. Postoperatively, all patients were asymptomatic and their recovery was uneventful. CONCLUSIONS: Our initial experience indicates that MIDCAB offers good results and is a treatment option for selected patients with left anterior descending and/or right coronary artery lesions.