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Biomedical subjects

A Yuan

Publications and source records attributed to A Yuan.

At least 73 records · Page 4Linked to original sources

Dicarboxylic acid dipeptide neutral endopeptidase inhibitors.

The synthesis of three series of dicarboxylic acid dipeptide neutral endopeptidase 24.11 (NEP) inhibitors is described. In particular, the amino butyramide 21a exhibited potent NEP inhibitory activity (IC50 = 5.0 nM) in vitro and in vivo. Blood levels of 21a were determined using an ex vivo method by measuring plasma inhibitory activity in conscious rats, mongrel dogs, and cynomolgus monkeys. Free drug concentrations were 10-1500 times greater than the inhibitory constant for NEP over the course of a 6 h experiment. A good correlation of free drug concentrations was obtained when comparing values determined by the ex vivo analysis to those calculated from direct HPLC measurements. Plasma atrial natriuretic factor (exogenous) levels were elevated in rats and dogs after oral administration of 19a. Urinary volume and urinary sodium excretion were also potentiated in anesthetized dogs treated with 21a.

Amino Acid Sequence↗

Transthoracic needle biopsy of thoracic tumours by a colour Doppler ultrasound puncture guiding device.

BACKGROUND: Ultrasound guided transthoracic needle aspiration biopsy has recently been used to obtain specimens for histological diagnosis of pulmonary and mediastinal tumours. Conventional real time, grey scale puncture guiding devices cannot differentiate vascular structures, and clear visualisation of the needle shaft or tip within a desired target is not always possible. This study describes a new built-in colour Doppler ultrasound puncture guiding device and assesses the relative safety of transthoracic needle aspiration biopsy of thoracic tumours by grey scale or colour Doppler ultrasound guidance. METHODS: Thirty patients with radiographic evidence of pulmonary (22 patients) or mediastinal tumours (eight patients) underwent ultrasonographic evaluation and transthoracic needle aspiration biopsy by using the colour Doppler ultrasound puncture guiding device (Aloka UST 5045P-3.5). These tumours were initially examined by grey scale ultrasound, and colour Doppler imaging was then used to evaluate the number of blood vessels surrounding and within the target tumour and the possibility of visualisation of the needle shaft or needle tip during the aspiration biopsy procedure. RESULTS: The colour Doppler ultrasound guiding device was far superior to the grey scale device for identification of the number of vessels surrounding or within the target tumour (83% v 20%) and for visualisation of the needle shaft or needle tip (80% v 17%). CONCLUSIONS: By using the colour Doppler ultrasound puncture device, vascular structures surrounding or within the target tumour can be verified. Visualisation of the needle shaft or tip is also better. Biopsy routes can be selected to avoid puncturing vessels. This approach should be particularly helpful for guiding biopsies of mediastinal tumours, where puncturing the heart or great vessels is a potential complication.

Adult↗

Tumor angiogenesis correlates with histologic type and metastasis in non-small-cell lung cancer.

This study investigated the clinico-pathologic correlation of tumor angiogenesis in non-small-cell lung cancers. Formalin-fixed, paraffin-embedded surgical specimens of 55 consecutive patients with primary non-small-cell lung cancers were examined. Included were 26 squamous cell carcinomas and 29 adenocarcinomas. Twenty-five patients had stage I disease, eight patients had stage II disease, and 22 patients had stage IIIA or IIIB disease. Among them, 28 had nodal metastasis and 27 did not. The microvessel was demonstrated by immunocytochemical staining for factor VIII and platelet endothelial cell adhesion molecules (PECAM-1). The microvessels in the areas of highest neovascularization were counted under light microscopy in 200x field by two independent observers without knowledge of clinical information. At least three separate fields were counted for each specimen. The Mann-Whitney U test was used for statistical analysis. The microvessel counts in adenocarcinoma were significantly higher than in the squamous cell carcinoma (54.4 +/- 35.65 versus 26.16 +/- 20.46 in factor VIII staining and 80.52 +/- 48.42 versus 40.04 +/- 32.33 in PECAM-1 staining; p < 0.001). The microvessel counts in patients with Stages I-II disease were significantly lower than that of stages IIIA-IIIB disease (23.63 +/- 16.21 versus 65.36 +/- 31.92 in factor VIII staining and 41.85 +/- 36.76 versus 93.00 +/- 43.08 in PECAM-1; p < 0.001). Patients with nodal metastasis had higher microvessel density than those without nodal metastasis (56.67 +/- 35.55 versus 23.44 +/- 15.77 in factor VIII staining and 86.89 +/- 46.46 versus 36.30 +/- 25.83 in PECAM-1 staining; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

The biologic window for chimeric L6 radioimmunotherapy.

BACKGROUND: There has been little success in using radioimmunotherapy in patients with adenocarcinoma, partly because of the low tumor uptake of the administered monoclonal antibody (MoAb). The authors recently reported therapeutic response in advanced cancer patients who received 131I chimeric-L6 MoAb. The L6 MoAb identifies abundant, nonshed antigen that is expressed in many human carcinomas, including carcinomas of the lung, breast, colon, and ovary. In vitro both mouse L6 (L6) and chimeric L6 (ChL6) mediate complement-dependent tumor cytolysis with human serum, and antibody-dependent tumor cell cytolysis with normal human peripheral blood mononuclear cells. The authors have used L6 or ChL6 for radioimmunotherapy to exploit their biologic activity to create a "therapeutic window" of increased vascular permeability, allowing more 131I MoAb to reach the tumor. A reactive target is present in the vascular endothelium but can be covered by unlabeled L6 or ChL6. METHODS: Nine patients with metastatic breast cancer were treated on a therapy protocol and received imaging and therapy doses of 131I ChL6 on two sequential days at 4 week intervals. During each treatment cycle, serum cytokines, complement, albumin, and 131I ChL6 blood clearance were monitored, peripheral blood mononuclear cell activation was assessed, and tumor uptake and response were documented. RESULTS: After L6 or ChL6 was infused, patients demonstrated immediate serum-complement activation, manifested by rapidly decreasing levels of serum complements 3 and 4. Tumor uptake of the second 131I MoAb (therapeutic) injection, given after the second daily injections of 200 mg MoAb, was usually higher than the tumor uptake of the first 131I MoAb (imaging) dose given after a single 200 mg infusion of MoAb. Although serum complement frequently decreased after the first 50-100 mg dose of L6 or ChL6, elevation of soluble interleukin-2 receptor (IL-2R) in serum was seen only in patients who received 150 mg or more of L6 or ChL6. In the nine treated patients, with only one exception, the higher grade of therapeutic tumor response was seen in patients with a greater increase in IL-2R levels. CONCLUSIONS: The clinical importance of understanding these mechanisms is emphasized by the occurrence of measurable tumor regressions in five of the first nine advanced metastatic breast cancer patients treated in this manner. Absence of pulmonary edema and delayed release of dose-dependent IL-2R suggest that targeting of the pulmonary endothelium by L6 or ChL6 is not the major cause of the observed biologic effects. This unique response of a solid tumor to radioimmunoconjugate therapy may be secondary to both the increased delivery of the radioimmunoconjugate to tumor cells caused by enhanced vascular permeability, and to synergistic effects of radiation and activated effector cell mechanisms.

Adult↗

Superior vena cava syndrome. Rapid histologic diagnosis by ultrasound-guided transthoracic needle aspiration biopsy.

We prospectively analyzed the diagnostic yield and safety of ultrasound (US)-guided transthoracic needle aspiration biopsy in the histologic diagnosis of 40 patients with superior vena cava (SVC) syndrome. During a 4-yr period, 40 patients with SVC obstruction were admitted to National Taiwan University Hospital. Of these patients 10 had histologic confirmation by sputum cytology (3 patients), fiberoptic bronchoscopy with biopsy (2 patients), or lymph node biopsy (5 patients) at admission. A total of 30 undiagnosed patients underwent real-time ultrasonographic (US) evaluation as well as color Doppler imaging. Patients with tumor detectable by US underwent US-guided transthoracic needle aspiration biopsy. Of the 30 patients who received US chest examination, 29 had widening of the upper mediastinal shadows in the chest radiographs. In 27 patients tumors were detected by chest US. After assessment of collateral vessels by color Doppler US, these 27 patients underwent US-guided transthoracic needle aspiration biopsies; histologic diagnoses were confirmed in 25. The diagnostic yield was 83.3%. The mean duration from admission to histologic diagnosis was 2.1 days. None of the patients developed complications. We conclude that chest US and color Doppler images are useful tools for evaluation of patients with SVC syndrome. US-guided transthoracic needle aspiration biopsy appears to be a safe, effective, and rapid approach for obtaining an accurate histologic diagnosis. Specific treatment can thus be initiated without delay.

Adult↗

Image comparison of real-time gray-scale ultrasound and color Doppler ultrasound for use in diagnosis of minimal pleural effusion.

To assess the value of color Doppler ultrasound in distinguishing minimal pleural effusion from pleural thickening, a prospective analysis was done on the ultrasonographic findings in 51 patients. Real-time, gray-scale, and color Doppler chest ultrasound examinations were carried out by different sonographers who had no clinical information concerning the patients. The sonographer evaluated the images for internal echogenicity of the effusion, pleural lesions that change shape with respiration, and movable septa and echo-densities in pleural space in conventional gray-scale as well as color signal in color Doppler ultrasound. Of the 35 patients with true effusion, 33 had positive color signal (sensitivity 94.3%, 95% confidence intervals [CI] 89 to 98.6%); in 16 patients without effusion, none had color signal (specificity 100%, 95% CI 83 to 100%). Although real-time, gray-scale ultrasound is also sensitive for detecting minimal effusion (sensitivity 100%, 95% CI 92 to 100%), it is less specific (specificity 68.7%, 95% CI 46 to 91.5%). Five of 16 examinations showing fluid-like lesions were found to be deceptive. With relatively high sensitivity and specificity, this method proved to be a useful diagnostic aid to real-time, gray-scale ultrasound for diagnosis of minimal or loculated effusion.

Adolescent↗

Differentiation of benign and malignant cervical lymph nodes with color Doppler sonography.

OBJECTIVE: This study proposed to evaluate the efficacy of color Doppler sonography in detecting possible differences in blood flow patterns between malignant and benign cervical lymph nodes. SUBJECTS AND METHODS: During a period of 12 months, the palpable cervical lymph nodes of 48 untreated patients were prospectively evaluated with color Doppler sonography and Doppler flow wave analysis. Histopathologic diagnoses were obtained by sonographically guided fine-needle aspiration biopsy and/or excisional biopsy. RESULTS: We found 16 benign lymph nodes (four were tuberculous lymphadenitis, four were reactive hyperplasia, and eight were unspecified) and 32 malignant lymph nodes (13 were squamous cell carcinomas, nine were adenocarcinomas, four were small-cell carcinomas, three were lymphomas, and three were miscellaneous). Color Doppler flow patterns were seen in six (38%) of the 16 benign lymph nodes and in 29 (91%) of the 32 malignant lymph nodes. Twenty-six (81%) of the 32 malignant lymph nodes had abnormal flow patterns, with resistance indexes less than 0.6. However, three (19%) of the 16 benign lymph nodes also had abnormal flow patterns, and only seven (54%) of 13 squamous cell carcinomas had abnormal flow patterns. CONCLUSION: Color Doppler sonography has limited clinical value in differentiating malignant from benign cervical lymph nodes and in obviating biopsy.

Adenocarcinoma↗

Color Doppler sonography of benign and malignant pulmonary masses.

OBJECTIVE: The purpose of this study was to compare blood flow in benign and malignant pulmonary masses by assessing the spectral waveforms obtained during color Doppler sonography. SUBJECTS AND METHODS: Fifty lung cancers in 46 patients and 28 benign lung lesions in 28 patients were evaluated with color Doppler sonography. Spectral wave analysis of blood flow (specifically, the Doppler variables of pulsatility index, resistive index, peak systolic velocity, and end diastolic velocity) was used to determine the distal impedance of vessels in malignant and benign pulmonary lesions. RESULTS: The flow signal detection rates for lung cancers and benign pulmonary lesions were 64% and 79%, respectively. All lung cancers with detectable flow signals had either relatively low-impedance flows or arteriovenous shunting, unlike the benign lesions, which usually had relatively high-impedance flows. For lung cancers, the pulsatility index was 1.43 +/- 0.31, the resistive index was 0.52 +/- 0.13, peak systolic velocity was 0.17 +/- 0.07 m/sec, and end diastolic velocity was 0.07 +/- 0.03 m/sec. For benign lung lesions, the pulsatility index was 3.32 +/- 0.68, the resistive index was 0.90 +/- 0.06, peak systolic velocity was 0.28 +/- 0.09 m/sec, and end diastolic velocity was 0.03 +/- 0.01 m/sec. All four variables were significantly different (p < .001) between lung cancers and benign lung lesions. When a cutoff value of mean +/- 2 SD was used, the resistive index and pulsatility index were shown to be sensitive and specific for the diagnosis of lung cancer (sensitivity, specificity = 100%, 95% for resistive index; 97%, 95% for pulsatility index). Flow was detected less often in squamous cell carcinoma than in adenocarcinoma and small-cell carcinoma. CONCLUSION: We conclude that color Doppler sonography is useful for showing vascularity in pulmonary masses, and may be helpful in differentiating malignant from benign lung tumors.

Blood Flow Velocity↗

Planar gamma camera imaging and quantitation of yttrium-90 bremsstrahlung.

UNLABELLED: Yttrium-90 is a promising radionuclide for radioimmunotherapy of cancer because of its energetic beta emissions. Therapeutic management requires quantitative imaging to assess the pharmacokinetics and radiation dosimetry of the 90Y-labeled antibody. Conventional gamma photon imaging methods cannot be easily applied to imaging of 90Y-bremsstrahlung because of its continuous energy spectrum. METHODS: The sensitivity, resolution and source-to-background signal ratio (S/B) of the detector system for 90Y-bremsstrahlung were investigated for various collimators and energy windows in order to determine optimum conditions for quantitative imaging. After these conditions were determined, the accuracy of quantitation of 90Y activity in an Alderson abdominal phantom was examined. RESULTS: When the energy-window width was increased, the benefit of increased sensitivity outweighed degradation in resolution and S/B ratio until the manufacturer's energy specifications for the collimator were exceeded. Using the same energy window, we improved resolution and S/B for the medium-energy (ME) collimator when compared to the low-energy, all-purpose (LEAP) collimator, and there was little additional improvement using the high-energy (HE) collimator. Camera sensitivity under tissue equivalent conditions was 4.2 times greater for the LEAP and 1.7 times greater for the ME collimators when compared to the HE collimator. Thus, the best, most practical selections were found to be the ME collimator and an energy window of 55-285 keV. When we used these optimal conditions for image acquisition, the estimation of 90Y activity in organs and tumors was within 15% of the true activities. CONCLUSIONS: The results of this study suggest that reasonable accuracy can be achieved in clinical radioimmunotherapy using 90Y-bremsstrahlung quantitation.

Beta Particles↗

Ultrasound guided aspiration biopsy for pulmonary tuberculosis with unusual radiographic appearances.

BACKGROUND: Pulmonary tuberculosis can produce unusual radiographic appearances and negative results of sputum and bronchoscopic examinations are common. This study assessed the value of ultrasound guided aspiration biopsy in the diagnosis of pulmonary tuberculosis with unusual radiographic appearances. METHODS: Thirteen patients, ultimately diagnosed as having tuberculosis, underwent a chest ultrasonographic examination between June 1984 and August 1991. All had sputum available for examination and nine were also examined by bronchoscopy. Ten patients who had a negative sputum smear and negative bronchoscopic brushing smears underwent ultrasound guided aspiration or biopsy. Percutaneous aspiration was performed with a 22 gauge needle. If the smear did not reveal acid fast bacilli, a biopsy sample was taken with a 16 gauge Tru-cut needle to obtain a histological diagnosis. RESULTS: The ultrasonographic examination delineated the more complex nature of the lesions better than the chest radiograph. Ultrasound guided aspiration biopsy provided the diagnosis in nine of 10 patients, while the sputum smear and culture provided diagnosis in five of 13, and bronchoscopy in four of nine. In terms of rapid diagnosis, ultrasound guided aspiration biopsy gave the diagnosis in eight of 10 cases. No patient developed a major complication. CONCLUSION: Ultrasonography can direct the needle to the most suitable part of a lesion to obtain the relevant specimens. The diagnostic yield is high and the procedure is relatively safe. It is especially helpful in patients with negative results of sputum and bronchoscopic examinations.

Adolescent↗

Ultrasonography and color Doppler imaging of metastatic pulmonary choriocarcinoma.

Chest ultrasound and color Doppler flow imaging were used to assess the pulmonary nodule of a 24-year-old pregnant woman with dyspnea and hemoptysis. The ultrasonogram showed multiple hypoechoic subpleural nodules. Color Doppler imaging of the nodules revealed characteristics of high vascularity and high blood flow. A percutaneous needle aspiration under ultrasonic guidance confirmed the diagnosis of choriocarcinoma.

Adult↗

Radioiodinated anti-hepatocellular carcinoma (HCC) ferritin. Targeting therapy, tumor imaging and anti-antibody response in HCC patients with hepatic arterial infusion.

Radioimmunoimaging and radioimmunotherapy with radioiodinated anti-(hepatocellular carcinoma ferritin) antibody (131I- or 125I-FtAb) have been applied in patients with primary liver cancer. A total of 41 patients with surgically unresectable hepatocellular carcinoma (HCC) and receiving hepatic artery ligation and cannulation during exploratory laparotomy were treated with this regimen by intrahepatic arterial infusion. Compared with the control group, a decline of serum alpha-fetoprotein (65.7% versus 42.9%) and shrinkage of tumor (68.3% versus 33.9%) were observed in the treated group, and a higher second-look resection rate (31.7% versus 5.1%) and longer survival (1-year: 61.0% versus 37.3%, 3-year: 25.0% versus 6.9%) resulted. The administration of antibody through a hepatic arterial catheter (n = 16) was compared with intravenous injection (n = 17) in terms of the tumor-imaging sensitivity in 33 patients with liver cancer. The results indicated that hepatic arterial infusion was superior to intravenous injection. The sensitivity 7 days after the administration was 100% in the i.a. group and 76.5% in the i.v. group, the uptake ratio of tumor to liver being 1.74 +/- 0.57 in the former and 1.34 +/- 0.29 in the latter. Furthermore, intrahepatic arterial infusion revealed a lower anti-antibody detection rate than intravenous injection (0/14 versus 4/11).

Antibody Formation↗

Ultrasound-guided aspiration biopsy of small peripheral pulmonary nodules.

We compared the diagnostic yields of ultrasound-guided aspiration biopsy, sputum cytology, and fiberoptic bronchoscopy with biopsy in 30 patients with peripheral pulmonary nodules smaller than 3.0 cm in diameter. Among them, there were 4 minute nodules with diameter less than 1.0 cm, 12 between 1.1 to 2.0 cm, and 14 between 2.1 to 3.0 cm. The final diagnoses in these 30 patients, as confirmed by histologic findings, microbiology, and clinical follow-up, revealed 24 malignant lesions and 6 benign. All of these 30 nodules received ultrasound-guided transthoracic fine-needle aspiration biopsy, and confirmative diagnoses were obtained in 27 (90 percent). Twenty-two (92 percent) of 24 patients with malignant nodules had positive cytology for malignancy and 5 (83 percent) of 6 patients with benign lesions had diagnosis made by cytologic and microbiologic examinations. One patient developed asymptomatic pneumothorax after needle aspiration. The size of the lesions did not affect the diagnostic yield and complication rate. None of the lesions was diagnosed by sputum cytology (0 of 19; 0 percent). Two patients had diagnoses obtained by fiberoptic bronchoscopy with biopsy (2 of 10; 20 percent). We conclude that ultrasound-guided aspiration biopsy is a useful and safe method for diagnosis of peripheral pulmonary nodules, even when the size of the nodule is less than 3 cm in diameter. The diagnostic yield far exceeds that which can be obtained by sputum cytology and fiberoptic bronchoscopy with biopsy.

Adult↗

Actinobacillus actinomycetemcomitans pneumonia with chest wall involvement and rib destruction.

There are four cases of Actinobacillus actinomycetemcomitans pulmonary infections reported in the English literature prior to 1990. We report a case of A actinomycetemcomitans pulmonary infection with invasion of overlying soft tissue, rib, and sternum. This manifestation has not been previously reported. The clinical manifestation is similar to that of Actinomyces israelii, which may be misinterpreted as malignancy initially. The portal of entry of A actinomycetemcomitans may be via hematogenous spread or aspiration. The diagnosis depends on culture after prolonged incubation of the involved tissue obtained by aspiration or biopsy. Elevated serum antibody is helpful for diagnosis of active infection. A actinomycetemcomitans is susceptible to most antibiotics, but is frequently resistant to penicillin, vancomycin, clindamycin, and erythromycin. Isolation of the organism and an in vitro drug sensitivity testing are important in managing the patient. Our patient recovered after a three-month regimen of penicillin.

Actinobacillus Infections↗

Lung sequestration. Diagnosis with ultrasound and triplex Doppler technique in an adult.

The application of chest US with triplex Doppler technique to detect the systemic feeding artery of lung sequestration in an adult patient is described. To our best knowledge, this is the first description of the use of this technique to diagnose pulmonary sequestration in adult patients. This 35-year-old man had necrotizing pneumonia with abscess formation at the left lower lobe. Chest US demonstrated a large tortuous vessel in the central part of the lesion. Spectral wave Doppler analysis showed that this vessel was a systemic feeding artery and had pulsatile arterial wave-form. The color Doppler mapping delineated the blood flow originating from the descending aorta and toward the lesion, thus confirming the diagnosis of pulmonary sequestration. We conclude that chest US with triplex Doppler technique is a valuable method in evaluating a patient with a pulmonary lesion who was thought to have lung sequestration before performing invasive aortography.

Adult↗