Additional pregnane glycoside from Baseonema acuminatum.

The isolation of baseonemoside C (1), a new pregnane glycoside from the aerial parts of Baseonema acuminatum is reported.

Glucolipsin A and B, two new glucokinase activators produced by Streptomyces purpurogeniscleroticus and Nocardia vaccinii.

During the screening of the natural products for their ability to increase the activity of glucokinase by relieving inhibition by long chain fatty acyl CoA esters (FAC), two novel compounds, glucolipsin A (1) and B (2) were isolated from the butanol extracts of Streptomyces purpurogeniscleroticus WC71634 and Nocardia vaccinii WC65712, respectively. The structures of these two compounds were established by spectroscopic methods and chemical degradation. Glucolipsin A (1) and B (2) relieved the inhibition of glucokinase by FAC with RC50 values of 5.4 and 4.6 microM.

Quanolirones I and II, two new human cytomegalovirus protease inhibitors produced by Streptomyces sp. WC76535.

Two new naphthacenequinone glycosides, quanolirones I (1) and II (2) were isolated, together with the known compound galtamycin from the fermentation broth of Streptomyces sp. WC76535. The structures 1 and 2 were established by analysis of their spectroscopic data and by comparison of their data to those of galtamycin. Compounds 1, 2, and galtamycin showed inhibitory activity against HCMV protease with IC50 values of 14, 35, and 52 microM, respectively.

Scintimammographic analysis of nonpalpable breast lesions previously identified by conventional mammography.

BACKGROUND: In randomized trials, screening mammography has led to decreased mortality from breast cancer. However, the low positive predictive value of mammography (i.e., the proportion of patients with a positive test result who actually have breast cancer) results in a large number of unnecessary biopsies. We determined whether scintimammography with technetium-99m-sestamibi is a useful supplemental diagnostic tool for women with nonpalpable breast abnormalities identified by conventional mammography. METHODS: Scintimammography was performed preoperatively on 70 women who were 31-66 years of age (mean age and median age = 51 years). These women had nonpalpable breast abnormalities identified by conventional mammography; subsequently, a needle-localization excisional biopsy of each suspicious lesion was performed. Scintimammographic images were interpreted independently by two nuclear medicine physicians who were blinded to all clinical and pathologic data, and an interobserver variation analysis was performed. RESULTS: Interobserver variation analysis of the scintimammographic findings showed an agreement for breast diagnosis of 97% and a kappa coefficient of 0.90. Comparison of scintimammographic findings and histopathologic results revealed that the sensitivity (proportion of patients with breast cancer who had a positive test result), the specificity (proportion of patients without breast cancer who had a negative test result), the positive predictive value and the negative predictive value (proportion of patients with a negative test result who actually did not have breast cancer) of scintimammography were 56% (95% confidence interval [CI] = 23%-85%), 87% (95% CI = 75%-94%), 38% (95% CI = 15%-68%), and 93% (95% CI = 82%-98%), respectively. Four of nine breast cancers were not detected by scintimammography. CONCLUSION: Because of excellent interobserver agreement, scintimammography provides an objective way of detecting primary breast carcinoma. In view of its low sensitivity and positive predictive value, however, scintimammography is not currently recommended as a screening test in patients with nonpalpable positive mammographic findings.

Immunohistologic assessment of technetium-99m-MIBI uptake in benign and malignant breast lesions.

UNLABELLED: This study was undertaken to assess the relationship between the degree of 99mTc-MIBI uptake in breast lesions and the following histologic factors: neovascularity, desmoplastic reaction, cellular proliferation and mitochondrial density. METHODS: Forty-two patients who previously underwent MIBI breast imaging (4 false-negative, 12 false-positive, 15 true-negative, 11 true-positive) were studied. Immunohistochemical staining was performed for neovascularity (Factor VIII antigen), desmoplasia (alpha-actin antigen), mitochondrial density (mitochondrial antigen) and cellular proliferation (MIB-1 antigen). The degree of microscopic staining was correlated with region of interest measurements of MIBI uptake on scintigraphy. RESULTS: There was a poor correlation between MIBI uptake and the degrees of neovascularity (r = 0.08, p > 0.05) and intracellular mitochondrial density (r = 0.04, p > 0.05) while there was a moderate correlation with cellular proliferation (r = 0.4, p < 0.05) and desmoplasia (r = 0.55, p < 0.001). CONCLUSION: The degree of MIBI uptake in breast lesions is multifactorial, but it appears to be related more to the degree of desmoplastic activity and cellular proliferation than neovascularity and mitochondrial density.

Detection of axillary lymph node metastasis of breast carcinoma with technetium-99m sestamibi scintimammography.

Several investigators have advocated management of breast cancer patients without axillary dissection, obviating the morbidity associated with this procedure. Approximately 30-40 per cent of all patients with breast carcinoma will have lymph node metastasis. Axillary dissection offers no therapeutic benefit to node-negative patients, and it may lead to unnecessary morbidity. It is apparent that a noninvasive test to determine the presence of axillary metastases may obviate the need for axillary dissection. The aim of this study was to determine the role of scintimammography (SMM) with technetium-99m sestamibi in the detection of axillary node metastasis in breast carcinoma. Thirty-one women with the diagnosis of breast carcinoma who had SMM and axillary lymphadenectomy were included. SMM was done following an intravenous injection of 20 mCi of Tc-99m sestamibi. Planar scintigraphic imaging was acquired in a lateral prone and an anterior view of the breasts for the evaluation of the axilla. SMM scans were interpreted by two nuclear medicine physicians blinded to the clinical presentation and histologic results. The correlation of SMM with histologic assessment showed a sensitivity of 75 per cent, specificity of 82 per cent, positive predictive value of 88 per cent, and negative predictive value of 64 per cent. The interobserver correlation of SMM interpretation between the two nuclear medicine physicians showed good agreement, with kappa = 0.49. Consistency in the interpretation of Tc-99m SMM was obtained when two independent radiologists reviewed the studies. Based on these data, we are unable to show that SMM is a reliable test for the detection of axillary metastases in patients with breast cancer. However, a high positive value of 88 per cent is encouraging and deserves further study.

Scintimammography: the new role of technetium-99m Sestamibi imaging for the diagnosis of breast carcinoma.

Technetium-99-Sestamibi scintimammography has emerged as a new procedure for the imaging of breast tumors. Currently, a large clinical experience has been developed and the results published. At the present time, the major drawback of this procedure appears to be its low sensitivity for the detection of breast carcinomas smaller than 1 cm in diameter. There are other biologic and technical issues that remain to be overcome to optimally image the breasts. Some of these include: development of a dedicated breast imager using nuclear medicine techniques, development of stereotactic needle localization of the abnormalities that demonstrate focal increase uptake in women with normal mammogram and breast physical examination, manufacturing of a breast compression device so that we can immobilize the breast in place for more adequate imaging, overcoming the issue of unilateral or bilateral diffuse breast uptake that is noted in 7-10 percent of the cases and finally, determination of optimal dose and imaging factors. This review includes our experience at Harbor-University of California, Los Angeles Medical Center with the use of this agent for breast imaging since 1992.

Scintimammography with Tc-99m sestamibi.

Mammography and physical breast examination are currently the most frequently and recognized screening tools for detection of breast carcinoma. These methods have been proved successful for early detection of breast cancer. Considering the 85% sensitivity associated with combined mammography and physical examination and a low positive predictive value of 20%-30% for diagnosis of breast carcinoma, there is a critical need for a more accurate, noninvasive imaging test to improve the sensitivity and specificity of mammography (7, 19, 20). Since early 1992, we have studied over 1200 women with clinically and/or mammographic abnormalities prior to breast biopsy and/or fine needle aspiration cytology of the breast. We have evaluated the role of Tc 99m Sestamibi as a complimentary procedure to conventional mammography in detection of breast carcinoma. The preliminary results of our studies have been published elsewhere (14, 17, 18). DuPont Merck Pharmaceutical Company in the USA on that basis, determined to conduct a multicenter clinical trial for the role of this radiopharmaceutical for the diagnosis of breast carcinoma in women with mammographically and/or clinically palpable abnormalities. This study was conducted at 42 institutions throughout the United States and Canada enrolling 673 women who where otherwise scheduled for breast biopsy and/or mastectomy. The preliminary results of this trial in both palpable and nonpalpable breast abnormalities are encouraging (24). Our most recent study on 157 women (mean age 47.9 years +/- 10.2) with 164 lesions with indications for histologic and cytologic analysis who underwent scintimammography with Tc 99m Sestamibi demonstrated the sensitivity of 92.3% and the specificity 87.5% (15). We have concluded that Scintimammography with Tc 99m Sestamibi can be used in conjunction with mammography to improve its specificity.

Harziphilone and fleephilone, two new HIV REV/RRE binding inhibitors produced by Trichoderma harzianum.

During the screening of the natural products for their ability to inhibit the binding of REV (regulation of virion expression) protein to [33P] labeled RRE (REV responsive element) RNA, two novel fungal metabolites, harziphilone and fleephilone, were isolated from the butanol-methanol (1:1) extract of the fermentation broth of Trichoderma harzianum by bioassay guided fractionation. The structures of these two new compounds were established by spectroscopic methods. Harziphilone and fleephilone showed inhibitory activity against the binding of REV-protein to RRE RNA with IC50 values of 2.0 microM and 7.6 microM, respectively. However both compounds did not protect CEM-SS cells from acute HIV infection at concentration levels up to 200 micrograms/ml using an XTT dye reduction assay. In addition, harziphilone demonstrated cytotoxicity at 38 microM against the murine tumor cell line M-109.

Comparison of electron beam computed tomography scanning and magnetic resonance imaging quantification of right ventricular mass: validation with autopsy weights.

RATIONALE AND OBJECTIVES: We compared, in the same human hearts, the ability of magnetic resonance (MR) imaging and electron beam computed tomography (CT) scanning to accurately quantify the free wall and septal components of right ventricular (RV) mass. METHODS: Eleven hearts extracted at autopsy were subjected to MR imaging and electron beam CT scanning in short-axis projections. Regression analyses of mass determinations obtained by manual planimetry MR imaging and electron beam CT scanning and autopsy weights were performed. RESULTS: RV free wall mass by both MR imaging (53.4 +/- 19.1 g) and electron beam CT scanning (53.9 +/- 20.4 g) correlated well with autopsy weight (57.7 +/- 20.2 g). Regression analysis showed a strong correlation for MR imaging (r = .88, slope = .88, standard error the estimate [SEE] = 7.2 g, p < .001) and electron beam CT scanning (r = .95, slope = .95, SEE = 6.6 g, p < .001). RV septal mass by MR imaging (10.8 +/- 3.5 g) and electron beam CT scanning (7.1 +/- 2.4 g) correlated less well with the autopsy weight (12.5 +/- 6.5 g). Regression analysis showed a fair correlation for MR imaging (r = .45, slope = .83, SEE = 2.05 g, p = .001) and a poor correlation for electron beam CT scanning (r = .46, slope = .17, SEE = 2.25 g, p = .57). CONCLUSION: Both MR imaging and electron beam CT scanning accurately predict RV free wall mass but have difficulty predicting the septal component. Because the septal component constitutes only a small proportion of the total RV mass, determinations of RV mass should be based solely on the free wall component.

Niruriside, a new HIV REV/RRE binding inhibitor from Phyllanthus niruri.

During the screening of natural products for their ability to inhibit the binding of HIV-REV protein to [33P]-labeled RRE RNA, one novel compound, niruriside (1), was isolated from the MeOH extract of the dried leaf of Phyllanthus niruri L. by bioassay-guided fractionation. The structure of niruriside was determined by spectroscopic methods. Niruriside showed specific inhibitory activity against the binding of REV protein to RRE RNA with an IC50 value of 3.3 microM; however, niruriside did not protect CEM-SS cells from acute HIV infection at concentrations up to 260 microM using an XTT dye reduction assay.

Myocardial cysticercosis detected by ultrafast CT.

Cysticercosis can affect any organ of the body although central nervous system manifestations are the most common. Cysticercosis involving the myocardium is extremely rare and is usually diagnosed postmortem. We report a case of cysticercosis involving the myocardium diagnosed antemortem using ultrafast CT.

Tc-99m sestamibi and In-111 pentetreotide uptake in metastatic papillary thyroid carcinoma.

Approximately 25% of metastatic and recurrent differentiated (papillary and follicular) thyroid carcinoma do not concentrate 1-131 Nal. In such cases, diagnosis can be attempted with other radiopharmaceuticals. The authors present a case of recurrent papillary thyroid carcinoma that was well visualized with Tc-99m sestamibi and In-111 pentetreotide; but only poorly visualized by I-131 Nal.

Technetium-99m-sestamibi scintimammography of breast lesions: clinical and pathological follow-up.

UNLABELLED: Mammography and physical examination combined have a sensitivity of 85% for the detection of breast carcinoma. Mammography also has a positive predictive value of 15%-30%. The aim of this study was to evaluate the usefulness of scintimammography using 99mTc-sestamibi as a complementary technique to mammography for the detection of breast carcinoma to improve mammography's sensitivity and specificity. METHODS: We studied 100 consecutive patients (mean age 48.3 +/- 10.8 yr) who had 106 lesions warranting biopsy (67 lesions) or fine needle aspiration cytology (FNA) (39 lesions) of the breast. There were 85 palpable and 21 nonpalpable lesions. The size of the lesions on the mammograms were moderate (2.3 +/- 1.8 x 1.9 +/- 1.5 cm). Each patient received 20 mCi 99mTc-sestamibi intravenously. Five and 60 min postinjection, planar breast images in the lateral prone position were obtained. An anterior erect projection was then obtained to visualize the axilla and, if needed, a posterior oblique prone projection. RESULTS: Scintimammography was true-positive in 30 lesions with biopsy-confirmed breast carcinoma; it was true-negative in 65 lesions subsequently proved to be benign. There were nine breast lesions with benign findings in which the scintimammography result was positive (false-positive scintimammography) for cancer. Finally, two lesions with pathologically proven carcinomas demonstrated a negative scintimammographic result. Therefore, in this group, the sensitivity of scintimammography was 93.7% with a specificity of 87.8%; the positive predictive value was 76.9%. The negative predictive value was 97%. CONCLUSION: Scintimammography is a highly sensitive test that improves the specificity of conventional mammography for the detection of breast carcinoma.

Metastatic spread of cervical carcinoma to the right ventricle and pulmonary arteries: diagnosis by ultrafast computed tomography.

A case of previously undiagnosed cervical carcinoma metastatic to the right ventricular cavity and the central and peripheral pulmonary arteries is presented. The usefulness of ultrafast computed tomography in comparison with echocardiography for the evaluation of suspected metastatic diseases to the heart and pulmonary arteries is discussed.

BMS-192548, a tetracyclic binding inhibitor of neuropeptide Y receptors, from Aspergillus niger WB2346. II. Physico-chemical properties and structural characterization.

The structure of BMS-192548, a tetracyclic binding inhibitor of neuropeptide Y receptors, was established by spectroscopic methods. The compound has an unusual B-C-D ring beta-diketone moiety.

BMS-192548, a tetracyclic binding inhibitor of neuropeptide Y receptors, from Aspergillus niger WB2346. I. Taxonomy, fermentation, isolation and biological activity.

During the screening of microbial fermentation extracts for their ability to inhibit the binding of 125I-peptid YY (PYY) to the neuropeptide Y (NPY) receptor using the scintillation proximity assay (SPA), BMS-192548 was isolated from the extract of Aspergillus niger WB2346 by bioassay-guided fractionation. BMS-192548 showed the inhibitory activity against 125I-PYY binding to SK-N-MC and SMS-KAN cells, which express NPY1 and NPY2 receptors, respectively, with IC50 values of 24 microM in Y1 and 27 microM in Y2 receptor binding. BMS-192548 demonstrated weak cytotoxicity against murine tumor cell line M-109 with an IC50 value of 240 microM.

Scintimammography: the complementary role of Tc-99m sestamibi prone breast imaging for the diagnosis of breast carcinoma.

PURPOSE: To evaluate the complementary role of technetium-99m sestamibi scintimammography in improvement of the sensitivity and specificity of mammography in detection of carcinoma of the breast. MATERIALS AND METHODS: At 5 and 60 minutes after intravenous injection of Tc-99m sestamibi, scintimammograms were obtained in 147 women (age range, 18-73 years; mean age, 47.9 years +/- 10.2 [standard deviation]) with 153 lesions that warranted breast biopsy (102 lesions) or fine-needle aspiration cytologic analysis (51 lesions). There were 113 palpable and 40 nonpalpable lesions. Lesion size on mammograms was 0.8 x 0.6 cm to 15.0 x 11.0 cm (mean, 2.82 cm +/- 1.71 x 2.39 cm +/- 1.56). RESULTS: Scintimammographic findings were true-positive in 47 biopsy-confirmed carcinomas, true-negative in 91 benign lesions, false-positive in 11 lesions with benign histopathologic findings (fibrocystic disease [n = 8] or fibroadenoma [n = 3]), and false-negative in four lesions of infiltrating ductal carcinoma. The sensitivity of scintimammography was 92.2%; specificity, 89.2%; positive predictive value, 81.0%; and negative predictive value, 95.8%. CONCLUSION: The authors conclude that scintimammography is a sensitive test that can improve the detection of breast carcinoma.

Investigation of abnormal appearing thyroid glands on Tc-99m sestamibi breast scintimammography.

Of 507 breast scintimammograms performed using Tc-99m sestamibi, 34 patients were incidentally found to have abnormal appearing thyroid glands. The authors sought to investigate the clinical significance and/or ascertain an extraneous causative factor for these findings. One cold thyroid nodule was detected and was proven benign through biopsy. Two cases of subacute and chronic thyroiditis were proven, and it is possible that additional patients had this disease process. Focal areas of increased thyroid Tc-99m sestamibi uptake were observed in eight patients and probably represent parathyroid adenomas, nonautonomous hyperfunctioning thyroid nodules, or nontoxic multinodular goiter. The results did not yield an extraneous causative factor, underlying pathology, or clinically significant disease in all of the patients investigated, but the findings suggest a need for careful evaluation of any unusual uptake in the thyroid gland and the rest of the image. The authors do not recommend investigation of all abnormal appearing thyroid glands on Tc-99m sestamibi scintimammography. However, clinical correlation should be recommended.