[Coronary CT angiography derived fractional flow reserve: the consideration and practice of functional evaluation for cerebral arterial diseases].

Cerebrovascular disease is a significant global public health concern, despite the diagnosis and treatment of stroke has made great progress in recent years, however, its mainly guided by anatomical indicators, which still needs to be further improved, and there is an urgent need to explore a more accurate and comprehensive functional imaging assessment method. Rapid development of coronary CT angiography derived fractional flow reserve (CT-FFR) has become an important technique for noninvasive evaluation of coronary artery disease, and these successful application experiences inspiried neurologists to explore the functional evaluation technique of cerebral arteries and demonstrated broad application prospects. In this paper, by analyzing and comparing the coronary CT-FFR technology, the progress, existing problems and possible solutions of the functional evaluation for cerebral arterial stenosis are discussed from the aspects of coronary CT-FFR study, cerebral artery functional evaluation study, and the comparison and consideration of cerebral arterial and coronary CT-FFR.

Long-term effect of aromatase inhibitors on bone microarchitecture and macroarchitecture in non-osteoporotic postmenopausal women with breast cancer.

In non-osteoporotic postmenopausal women with breast cancer, aromatase inhibitors (AIs) negatively affected bone mineral density (BMD), lumbar spine trabecular bone score (TBS) as a bone microarchitecture index, and hip geometry as a bone macroarchitecture index. INTRODUCTION: AIs increase the risk of fracture in patients with breast cancer. Therefore, we aimed to evaluate the long-term skeletal effects of AIs in postmenopausal women with primary breast cancer. METHODS: We performed a retrospective longitudinal observational study in non-osteoporotic patients with breast cancer who were treated with AIs for ≥3 years (T-score >-2.5). Patients with previous anti-osteoporosis treatment or those who were given bisphosphonate during AI treatment were excluded from the analysis. We serially assessed BMD, lumbar spine TBS, and hip geometry using dual-energy X-ray absorptiometry. RESULTS: BMD significantly decreased from baseline to 5 years at the lumbar spine (-6.15%), femur neck (-7.12%), and total hip (-6.35%). Lumbar spine TBS also significantly decreased from baseline to 5 years (-2.12%); this change remained significant after adjusting for lumbar spine BMD. The annual loss of lumbar spine BMD and TBS slowed after 3 and 1 year of treatment, respectively, although there was a relatively constant loss of BMD at the femur neck and total hip for up to 4 years. The cross-sectional area, cross-sectional moment of inertia, minimal neck width, femur strength index, and section modulus significantly decreased, although the buckling ratio increased over the treatment period (all P < 0.001); these changes were independent of total hip BMD. CONCLUSIONS: Long-term adjuvant AI treatment negatively influenced bone quality in addition to BMD in patients with breast cancer. This study suggests that early monitoring and management are needed in non-osteoporotic patients with breast cancer who are starting AIs.

Sweat gland bioelectrics differ in cystic fibrosis: a new concept for potential diagnosis and assessment of CFTR function in cystic fibrosis.

BACKGROUND: For nearly 50 years the diagnosis of cystic fibrosis (CF) has depended on measurements of sweat chloride concentration. While the validity of this test is universally accepted, increasing diagnostic challenges and the search for adequate biomarker assays to support curative-orientated clinical drug trials have created a new demand for accurate, reliable and more practical CF tests. A novel concept is proposed that may provide a more efficient real-time method for assessing CFTR function in vivo. METHODS: Cholinergic and beta-adrenergic agonists were iontophoresed to stimulate sweating. The bioelectric potential from stimulated sweat glands (SPD) was measured in vivo using a standard ECG electrode applied to the skin surface. SPD and sweat chloride concentrations were compared in cohorts predicted to express a range of CFTR function as presented by healthy controls (HC), heterozygotes (Hz), pancreatic sufficient (CFPS) and pancreatic insufficient patients with CF (CFPI). RESULTS: The median SPD was hyperpolarized in patients with CF compared with control subjects (-47.4 mV vs -14.5 mV, p<0.001). In distinguishing between control and CF subjects, SPD (area under receiver operator curve (AUC) = 0.997) was similar to sweat chloride concentration (AUC = 0.986). Sequential cholinergic/beta-adrenergic sweat stimulation dramatically depolarised the SPD in patients with CF (p<0.001) but had no effect in control subjects (p = 0.6) or on the sweat chloride concentration in either group (p>0.5). Furthermore, the positive SPD response was larger in CFPI than in CFPS subjects (p = 0.04). CONCLUSION: These results support the concept that skin surface voltages arising from stimulated sweat glands can be exploited to assess expressed CFTR function in vivo and may prove to be a useful diagnostic tool.

Mullerian adenosarcoma with sarcomatous overgrowth of the cervix presenting as cervical polyp: a case report and review of the literature.

An aggressive variant of adenosarcoma, mullerian adenosarcoma with sarcomatous overgrowth (MASO) in the cervix is extremely rare. This variant contains obvious, high-grade sarcoma in addition to a low-grade form. In this report, we describe a case of MASO of the uterine cervix and review the clinical and pathological features of these tumors. The patient was a 37-year-old woman with a cervical polypoid mass, which was morphologically considered as a benign endocervical polyp. Microscopically, polypoid cervical mass showed diffuse and dense malignant spindle cell proliferation around the benign endocervical glands and also an area of markedly anaplastic and pleomorphic spindle cell proliferation, so called, sarcomatous overgrowth. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph node dissection were performed. The patient has been followed-up and neither chemotherapy nor other adjuvant therapies have been administered. At present, she has been clinically free of disease for 9 months since she received surgery. It is extremely rare that MASO of the uterine cervix is presented in premenopausal woman. Gynecologists and pathologists should be aware of the difficulties associated with a delay in the diagnosis of MASO when the tumor is present as a benign looking cervical polyp.

Expression of epidermal growth factor receptor in cervical tissue and serum in patients with cervical neoplasia.

OBJECTIVE: We hypothesized that there may be a relationship between epidermal growth factor receptor (EGFR) expression in cervical tissue and serum in patients with cervical neoplasia. MATERIALS AND METHODS: The expression of EGFR was measured in cervical tissues from 23 cervical intraepithelial neoplasia patients and 16 cervical carcinoma patients using immunohistochemical staining and the level of serum EGFR extracellular domain was measured in serum from 17 cervical intraepithelial neoplasia patients and 14 cervical carcinoma patients using enzyme-linked immunosorbent assay. RESULTS: The expression of EGFR was significantly increased as normal cervical tissue progressed to cervical intra-epithelial neoplasia then to cervical carcinoma (p = .009). The mean level of serum EGFR according to the intensity of immunohistochemical staining in negative, weakly positive, positive, and strongly positive staining was 19.36 +/- 3.12 fmol/mL, 20.99 +/- 3.59 fmol/mL, 29.08 +/- 16.86 fmol/mL, and 24.34 +/- 10.35 fmol/mL, respectively (p = .450). CONCLUSIONS: We believe that the level of serum EGFR may have a similar role as tumor markers such as the EGFR expression in cervical neoplastic tissue.

The behavior of a poly(aniline) solid contact pH selective electrode based on N,N,N',N'-tetrabenzylethanediamine ionophore.

A hydrogen ion-selective solid-contact electrode based on N,N,N',N'-tetrabenzylethanediamine has shown the best Nernstian slope and selectivity and the widest response range in a Tris buffered pH sample solution. Its linear dynamic range was pH 3.50-11.94, and the Nernstian slope showed 52.1 mV/pH (at 20 +/- 0.2 degrees C). When it was directly applied to human whole blood (in pH range 6.0-8.5) we could obtain the same satisfying results. This electrode continuously contacted a Tris 7.47 buffered solution, human whole blood and a hydrofluoric acid solution for one month without any loss of performance. Also, hydrofluoric acid did not influence the surface of this electrode, and thus it was maintained without showing any changes in potentials after being used in a hydrofluoric acid solution. The standard deviation in the determined e.m.f. differences was 1.5 mV (N = 5) for Tris buffer solutions of pH 6.5 and 1.1 mV at a Tris buffer solutions of pH 8.5. The 90% response time of the electrodes obtained by injecting of hydrochloric acid into the Tris buffer sample solution was less than 10 s. Especially, in the this paper, with these potential response characteristics of hydrogen ion selective poly(aniline) solid contact electrode, we have also presented the pH response mechanism of this electrode and the role of poly(aniline) and a doped anion in a poly(aniline) layer.

Effects of estrogen on nitric oxide synthase and histological composition in the rabbit clitoris and vagina.

We investigated the functional and histological changes after oophorectomy in the rabbit clitoris and vagina to determine the mechanism responsible for the development of arousal disorder in postmenopausal women. Twenty mature female New Zealand white rabbits were randomly divided into three groups: control; oophorectomy; and estrogen replacement after oophorectomy. We compared the nitric oxide synthase (NOS) activity and the degree of expression of neuronal (nNOS) and endothelial NOS (eNOS) using biochemical and Western blot analysis in clitoral and vaginal tissues. Histological change of smooth muscle and collagen contents in those tissues were also compared using Masson's trichrome staining. NOS activity and the expression of nNOS and eNOS were significantly increased in the oophorectomized group while there was a decrease to the level of the control group in the estrogen replacement group. Histological examination showed that oophorectomy induced a significant increase in collagen and decrease in muscle content in both clitoris and vagina, while the ratio of smooth muscle content was increased significantly after the estrogen replacement. Our results clearly demonstrate that estrogen deficiency induces compensatory NOS production which may be related to decreases in muscle to collagen ratio in female rabbit genital organs.

Epstein-Barr virus-associated peripheral T-cell lymphoma in adults with hydroa vacciniforme-like lesions.

We describe two Korean adult patients who had necrotizing papulovesicles mainly on their faces. Skin biopsy specimens showed perivascular and periadnexal infiltrate of atypical lymphoid cells with vasculitis in the dermis and subcutaneous tissue. In situ hybridization demonstrated a latent infection of Epstein-Barr virus in the majority of lymphoid cells in the dermis. These patients were diagnosed as having T-cell lymphoma. Interestingly, large granular lymphocytosis was found in the peripheral blood of Case 2.

Pathological findings in cumulative irritation induced by SLS and croton oil in hairless mice.

It is known that the pathological features of acute irritant contact dermatitis are specific according to the irritant. However, in chronic irritant contact dermatitis, it is not clear whether specific patterns exist. To investigate whether the specific pathology of acute irritant contact dermatitis is sustained in chronic irritant contact dermatitis, sodium lauryl sulfate (SLS) and croton oil were applied 3x a week for 2 weeks on the dorsal skin of hairless mice using Finn Chambers. The pathologic changes induced by irritants at various concentrations were evaluated using H&E and Luna's staining, as well as immunohistochemistry for 5-bromo-2-deoxyuridine (BrdU), keratin 6 and loricrin. Our results showed that epidermal hyperplasia and inflammatory infiltration were relatively marked in the groups treated with higher concentrations of irritants. These features were more prominent in the 1% croton oil treated group than in the 0.25% SLS treated group. However, lower concentrations of irritants resulted in very similar histological changes, characterized by epidermal hyperplasia with minimal inflammatory infiltration, irrespective of the chemical. Our results suggest that the histological responses to irritants vary with concentration in cumulative irritation, as in acute irritation, but repetitive mild irritation may evoke common histological changes, characterized by epidermal hyperplasia with minimal inflammatory infiltration, irrespective of the chemical used.

Potentiometric sensor for hydrogen ion based on N,N'-dialkylbenzylethylenediamine neutral carrier in a poly(vinyl chloride) membrane with polyaniline solid contact.

Hydrogen ion selective solid contact electrodes based on N,N'-dialkylbenzylethylenediamine (alkyl=butyl, hexyl, octy, decyl) are prepared. Solid contact electrodes and coated wire electrodes have been fabricated from polymer cocktail solutions based on N,N'-dialkylbenzylethylenediamine (alkyl=butyl, hexyl, octy, decyl). We showed that the response range and slopes are influenced by the alkyl chain length. Response ranges and Nernstian slops for solid contact electrodes were slightly better than for coated wire electrodes. Solid contact electrodes were shown linear selective to hydrogen ion in the pH ranges pH 4.5-13.0, 4.2-13.1, 3.4-13.0 and 3.0-13.2. and their Nernstian slopes were 49.7, 50.8, 51.5 and 53.7 mV pH(-1) at 20+/-0.2 degrees C, respectively. Stability is also improved especially when compared with coated wire electrodes. The 90% response time was <2 s and their electrical resistance varied in the range 2.37-2.76 MOmega. Especially solid contact electrodes with N,N'-didecylbenzylethylenediamine have shown the best selectivity and reproducibility of e.m.f..

Three-year follow-up of women with the sole diagnosis of depressive personality disorder: subsequent development of dysthymia and major depression.

OBJECTIVE: The authors sought to determine whether subjects with the sole diagnosis of depressive personality disorder are at higher risk for developing dysthymia and major depression than are healthy comparison subjects. METHOD: Eighty-five women with depressive personality disorder who had no comorbid axis I or axis II disorders and 85 age-matched healthy comparison women were initially recruited and reinterviewed 3 years later to evaluate the cumulative incidence rate of dysthymia and major depression. RESULTS: At the 3-year follow-up assessment, the women with depressive personality disorder had a significantly greater odds ratio for developing dysthymia than did the healthy comparison women. The difference in odds ratios for the development of major depression between women with and without depressive personality disorder did not reach statistical significance. CONCLUSIONS: The present study, the first to determine the subsequent development of dysthymia and major depression in subjects with the sole diagnosis of depressive personality disorder, found that subjects with depressive personality disorder had a greater risk of developing dysthymia than did healthy comparison subjects at 3-year follow-up. Findings of the current study also suggest that depressive personality disorder may mediate the effects of a family history of axis I unipolar mood disorders.

Identification of two novel frame shift mutations of the NF1 gene in Korean patients with neurofibromatosis type 1.

Neurofibromatos is type 1 (NF1) is one of the most common inherited disorders and is characterized by abnormalities in multiple tissues derived from the neural crest. The NF-1 gene has been cloned and mapped to human chromosome 17q11.2. The NF-1 gene has an open reading frame that predicts a protein consisting of 2,818 amino acids, known as neurofibromin. Here, we report two kinds of novel frame shift mutations of the NF1 gene from 2 out of 56 unrelated Korean NF1 patients. These mutations were detected using polymerase chain reaction and single strand conformational polymorphism analysis. Sequencing analysis revealed four base pair insertion at codon 1270 of exon 22, and a base pair deletion at codon 1398 of exon 24. These mutations resulted in premature termination of the mutant alleles and may encode truncated forms of neurofibromin.

Up-Regulation and redistribution of Bax in ultraviolet B-irradiated melanocytes.

Ultraviolet B (UVB) radiation may activate or deteriorate cultured human epidermal melanocytes, depending on the doses and culture conditions. It is also reported that cultured human epidermal melanocytes derived from different pigmentary phenotypes showed different responses to UVB radiation. In this study, we examined whether apoptosis of melanocytes can be induced by physiologic doses of UVB irradiation using cultured human epidermal melanocytes derived from oriental males of skin types III and IV. Propidium iodide staining for DNA condensation and flow cytometric analyses demonstrated the apoptotic cell death of melanocytes following UVB irradiation (0-30 mJ/cm2). The levels of p53, Bax, and Bcl-2, determined by immunoblotting, revealed a dose-dependent increase in p53 and Bax, but the level of Bcl-2 remained unchanged. Confocal microscopic examination showed that Bax moved from a diffuse to a punctate distribution after UVB irradiation. However, there were no changes in the pattern of distribution of Bcl-2. These data suggest that the high constitutional level of Bcl-2 may protect melanocytes from UVB-induced injury, and that apoptotic death of melanocytes may be induced by the elevation and redistribution of Bax.

Comparative quantitative analysis of ultraviolet B-induced skin blood flow change using laser Doppler perfusion imaging technique.

Laser Doppler perfusion imaging (LDI), recently developed, can generate a color-coded image of tissue perfusion, making it possible to assess the spatial distribution of skin perfusion without touching the surface. Using this apparatus, we investigated ultraviolet B (UVB)-induced perfusion profile of the skin and compared the results with those obtained from laser Doppler flowmetry (LDF). Fifteen adult male Korean volunteers were irradiated with several doses of UVB ranging from 25 mJ/cm2 to 186 mJ/cm2. Twenty-four hours later, the erythema reaction was evaluated with LDF and LDI systems. There was a significant correlation between the logarithmic dose of UVB and erythema values. The curves consisted of two parts, an initial, flat phase and then a linear, steep one. Also, there was a good correlation between LDF and LDI. The LDI is as sensitive as conventional LDF, but has the many advantages of measuring blood flow over large areas without contact with the skin surface. This instrument will be useful in the measurement of skin blood flow in many areas of dermatological application.

Pericarditis due to Tsutsugamushi disease.

Tsutsugamushi Disease is an acute febrile illness caused by Rickettsia tsutsugamushi, which enters into the human bloodstream through the bite of leptotrombidium. It is characterized by eschar, fever and cutaneous rash. Pericardial effusion in Tsutsugamushi Disease is not a common manifestation, although a high rate of effusion was reported in autopsy in those who had died of the disease. Here, we report a case of Tsutsugamushi pericarditis documented by indirect immunofluorescent test of pericardial fluid, and give a brief review of the literature.

Detection of transforming growth factor-alpha in the serum of gastric carcinoma patients.

Transforming growth factor-alpha (TGF-alpha) is a ligand for epidermal growth factor receptor (EGFR) and it is overexpressed in various malignancies including lung, esophageal, colorectal, ovarian and gastric carcinomas. In patients with gastric carcinoma, its overexpression may be associated with advanced stage or poor prognosis. We have recently demonstrated that the mean serum level for EGFR in gastric carcinoma patients was significantly elevated compared with that of healthy controls. Using the enzyme-linked immunosorbent assay, the levels of TGF-alpha were determined in serum from 40 patients with gastric carcinoma (5 patients with stage I, 2 stage II, 4 stage III, and 29 stage IV patients) and 33 healthy controls. The mean serum level for TGF-alpha in the gastric carcinoma patients was significantly elevated as compared with that of healthy controls (104 +/- 235 vs. 22 +/- 16 pg/ml; p = 0.03). Eleven patients with gastric carcinoma (27.5%) showed elevated serum TGF-alpha levels above the cutoff value of 54 pg/ml (defined as 2 standard deviations above the mean of the control group). No significant association was noted between the positivity of TGF-alpha and clinicopathologic characteristics including gender, age and stage. However, poorly differentiated adenocarcinoma showed a higher positivity of serum TGF-alpha (43.8%) compared with other histologic types, which was marginally significant (p = 0.06). These results suggest that serum TGF-alpha could be useful as a tumor marker of gastric carcinoma for predicting prognosis and follow-up after surgery in patients whose initial serum TGF-alpha levels are elevated.

Elevated serum levels of transforming growth factor-beta1 in patients with colorectal carcinoma: its association with tumor progression and its significant decrease after curative surgical resection.

BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) acts as a potent inhibitor of cell growth and tumor progression but loss of this negative regulation can contribute to tumor development. Some studies have reported an association between disease progression and TGF-beta1 expression in patients with colorectal carcinoma, but their results were not always consistent. METHODS: Serum levels of TGF-beta1 were measured using an enzyme-linked immunoadsorbent assay in 121 consecutive patients with colorectal carcinoma and compared with TGF-beta1 serum levels in 31 healthy volunteers. Serum levels of TGF-beta1 also were measured in 50 patients who underwent curative surgical resection (part of the 121 preoperative patients) to compare their levels with preoperative serum levels of TGF-beta1. RESULTS: Serum levels of TGF-beta1 in patients with colorectal carcinoma (45+/-15 ng/mL) (mean+/-the standard deviation) were significantly higher than those in the healthy control group (32+/-4 ng/mL) (P = 0.001). Serum levels of TGF-beta1 increased with increasing tumor stage (P < 0.01). Serum levels of TGF-beta1 were correlated significantly with depth of tumor invasion, lymph node metastasis, distant metastasis, and serum levels of carcinoembryonic antigen (CEA). Serum levels of TGF-beta1 tended to increase with increasing CEA (correlation coefficient = 0.21; P < 0.05). The mean serum level of TGF-beta1 in patients with colorectal carcinoma before surgery (45+/-14 ng/mL) (n = 50) significantly decreased to 34+/-7 ng/mL, which was within the normal range (32+/-4 ng/mL), after curative surgical resection of the tumor (P = 0.0000). Serum levels of TGF-beta1 after tumor resection decreased more significantly in patients with higher preoperative levels of TGF-beta1 (from 53+/-12 ng/mL to 36+/-6 ng/mL) (n = 30). CONCLUSIONS: The results of the current study suggest that serum levels of TGF-beta1 in colorectal carcinoma patients may be associated with disease progression and may be used as a biomarker in the management of colorectal carcinoma patients. The authors believe further studies with a large number of patients for a longer follow-up period are necessary to conclude whether serum levels of TGF-beta1 carry significant clinical relevance.